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Moore MR, DeClouette B, Wolfe I, Kingery MT, Sandoval-Hernandez C, Isber R, Kirsch T, Strauss EJ. Levels of Synovial Fluid Inflammatory Biomarkers on Day of Arthroscopic Partial Meniscectomy Predict Long-Term Outcomes and Conversion to TKA: A 10-Year Mean Follow-up Study. J Bone Joint Surg Am 2024; 106:2330-2337. [PMID: 39264991 DOI: 10.2106/jbjs.23.01392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/14/2024]
Abstract
BACKGROUND The purpose of the present study was to evaluate the relationships of the concentrations of pro- and anti-inflammatory biomarkers in the knee synovial fluid at the time of arthroscopic partial meniscectomy (APM) to long-term patient-reported outcomes (PROs) and conversion to total knee arthroplasty (TKA). METHODS A database of patients who underwent APM for isolated meniscal injury was analyzed. Synovial fluid had been aspirated from the operatively treated knee prior to the surgical incision, and concentrations of pro- and anti-inflammatory biomarkers (RANTES, IL-6, MCP-1, MIP-1β, VEGF, TIMP-1, TIMP-2, IL-1RA, MMP-3, and bFGF) were quantified. Prior to surgery and again at the time of final follow-up, patients were asked to complete a survey that included a visual analog scale (VAS) for pain and Lysholm, Tegner, and Knee injury and Osteoarthritis Outcome Score-Physical Function Short Form (KOOS-PS) questionnaires. Clustering analysis of the 10 biomarkers of interest was carried out with the k-means algorithm. RESULTS Of the 82 patients who met the inclusion criteria for the study, 59 had not undergone subsequent ipsilateral TKA or APM, and 43 (73%) of the 59 completed PRO questionnaires at long-term follow-up. The mean follow-up time was 10.6 ± 1.3 years (range, 8.7 to 12.4 years). Higher concentrations of individual pro-inflammatory biomarkers including MCP-1 (β = 13.672, p = 0.017) and MIP-1β (β = -0.385, p = 0.012) were associated with worse VAS pain and Tegner scores, respectively. K-means clustering analysis separated the cohort of 82 patients into 2 groups, one with exclusively higher levels of pro-inflammatory biomarkers than the second group. The "pro-inflammatory phenotype" cohort had a significantly higher VAS pain score (p = 0.024) and significantly lower Lysholm (p = 0.022), KOOS-PS (p = 0.047), and Tegner (p = 0.009) scores at the time of final follow-up compared with the "anti-inflammatory phenotype" cohort. The rate of conversion to TKA was higher in the pro-inflammatory cohort (29.4% versus 12.2%, p = 0.064). Logistic regression analysis demonstrated that the pro-inflammatory phenotype was significantly correlated with conversion to TKA (odds ratio = 7.220, 95% confidence interval = 1.028 to 50.720, p = 0.047). CONCLUSIONS The concentrations of synovial fluid biomarkers on the day of APM can be used to cluster patients into pro- and anti-inflammatory cohorts that are predictive of PROs and conversion to TKA at long-term follow-up. LEVEL OF EVIDENCE Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Michael R Moore
- NYU Langone Orthopedic Hospital, NYU Langone Health, New York, NY
| | | | - Isabel Wolfe
- NYU Langone Orthopedic Hospital, NYU Langone Health, New York, NY
| | | | | | - Ryan Isber
- NYU Langone Orthopedic Hospital, NYU Langone Health, New York, NY
| | - Thorsten Kirsch
- NYU Langone Orthopedic Hospital, NYU Langone Health, New York, NY
- Department of Biomedical Engineering, NYU Tandon School of Engineering, New York, NY
| | - Eric J Strauss
- NYU Langone Orthopedic Hospital, NYU Langone Health, New York, NY
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Tagliero AJ, Miller MD. Anterior Cruciate Ligament Tears in Soccer Players. Sports Med Arthrosc Rev 2024; 32:138-145. [PMID: 39087703 DOI: 10.1097/jsa.0000000000000391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/02/2024]
Abstract
Anterior cruciate ligament (ACL) injuries to soccer players present unique challenges in sports medicine, given the sport's global prevalence and intricate injury dynamics. These injuries, especially in the youth and female demographic, have become a substantial concern in sports medicine. This review explores the epidemiology, mechanism of injury, diagnostic procedures, treatment modalities, and rehabilitation strategies related to ACL tears within the soccer community. Progress in diagnostics, treatments, and rehabilitation underscores the importance of evidence-based approaches. As soccer continues its ascent in popularity, addressing the specific risks and nuances of ACL injuries in this context remains of paramount significance.
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Affiliation(s)
- Adam J Tagliero
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN
| | - Mark D Miller
- Department of Orthopedic Surgery, University of Virginia Health System, Charlottesville, VA
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Leite CBG, Smith R, Lavoie-Gagne OZ, Görtz S, Lattermann C. Biologic Impact of Anterior Cruciate Ligament Injury and Reconstruction. Clin Sports Med 2024; 43:501-512. [PMID: 38811124 DOI: 10.1016/j.csm.2023.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
Surgical intervention after anterior cruciate ligament (ACL) tears is typically required because of the limited healing capacity of the ACL. However, mechanical factors and the inflammatory response triggered by the injury and surgery can impact patient outcomes. This review explores key aspects of ACL injury and reconstruction biology, including the inflammatory response, limited spontaneous healing, secondary inflammation after reconstruction, and graft healing processes. Understanding these biologic mechanisms is crucial for developing new treatment strategies and enhancing patient well-being. By shedding light on these aspects, clinicians and researchers can work toward improving quality of life for individuals affected by ACL tears.
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Affiliation(s)
- Chilan B G Leite
- Department of Orthopaedic Surgery, Center for Cartilage Repair and Sports Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Richard Smith
- Department of Orthopaedic Surgery, Center for Cartilage Repair and Sports Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Ophelie Z Lavoie-Gagne
- Department of Orthopaedic Surgery, Center for Cartilage Repair and Sports Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Simon Görtz
- Department of Orthopaedic Surgery, Center for Cartilage Repair and Sports Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
| | - Christian Lattermann
- Department of Orthopaedic Surgery, Center for Cartilage Repair and Sports Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
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De Marziani L, Orazi S, Boffa A, Andriolo L, Di Martino A, Zaffagnini S, Filardo G. Knee temperature remains abnormal in patients successfully treated with anterior cruciate ligament reconstruction: An infrared thermography analysis. J Exp Orthop 2024; 11:e70012. [PMID: 39253542 PMCID: PMC11382133 DOI: 10.1002/jeo2.70012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 09/11/2024] Open
Abstract
Purpose The aim of this study was to evaluate if the operated knee environment remains abnormal in patients successfully treated with anterior cruciate ligament reconstruction (ACL-R). Methods Thirty asymptomatic patients were enrolled (28 men, 2 women, age 28.6 ± 6.54 years, body mass index: 24.9 ± 3.0 kg/m2) and evaluated at 42.2 ± 12.5 months after surgery. Patients were assessed with patient-reported outcome measurements and with a triaxial accelerometer. The temperature of the knees as well as four regions of interest were evaluated with an infrared thermographic camera FLIR T1020 (FLIR® Systems) according to a standardised protocol including a baseline evaluation and further evaluations immediately after exercise and after 5, 10 and 20 min. The temperature of the ACL-R knee was compared to that of the contralateral healthy knee for the purpose of the study. Results The mean temperature of the knee was higher (p = 0.010) for the ACL-R knees (31.4 ± 1.4°C) compared to the healthy knees (31.1 ± 1.6°C), as well as for the patellar area (p = 0.005), the lateral area (p = 0.016) and the medial area (p = 0.014). The analysis of the response to the exercises of the ACL-R knees showed similar trends to the healthy knees but higher temperature values at all time points (p < 0.05). Patients who underwent ACL-R with concomitant meniscal treatment showed higher knee temperatures compared to ACL-R knees without concomitant meniscal treatment after 5 (p = 0.047), 10 (p = 0.027) and 20 min (p = 0.048). Conclusions The temperature of asymptomatic knees previously treated with ACL-R is higher than the contralateral healthy knee, both at rest and after exercise, with a further increase in knees that underwent both ACL-R and meniscal treatment. These results suggest an inflammatory state persisting years after the surgery, which could predispose to the early onset of knee degeneration. Level of Evidence III, Case-control study.
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Affiliation(s)
- Luca De Marziani
- Clinica Ortopedica e Traumatologica 2 IRCCS Istituto Ortopedico Rizzoli Bologna Italy
| | - Simone Orazi
- Clinica Ortopedica e Traumatologica 2 IRCCS Istituto Ortopedico Rizzoli Bologna Italy
| | - Angelo Boffa
- Clinica Ortopedica e Traumatologica 2 IRCCS Istituto Ortopedico Rizzoli Bologna Italy
| | - Luca Andriolo
- Clinica Ortopedica e Traumatologica 2 IRCCS Istituto Ortopedico Rizzoli Bologna Italy
| | - Alessandro Di Martino
- Clinica Ortopedica e Traumatologica 2 IRCCS Istituto Ortopedico Rizzoli Bologna Italy
| | - Stefano Zaffagnini
- Clinica Ortopedica e Traumatologica 2 IRCCS Istituto Ortopedico Rizzoli Bologna Italy
| | - Giuseppe Filardo
- Applied and Translational Research (ATR) Center IRCCS Istituto Ortopedico Rizzoli Bologna Italy
- Faculty of Biomedical Sciences Università della Svizzera Italiana Lugano Switzerland
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Zsidai B, Kaarre J, Narup E, Samuelsson K. Timing of Anterior Cruciate Ligament Surgery. Clin Sports Med 2024; 43:331-341. [PMID: 38811113 DOI: 10.1016/j.csm.2023.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
This narrative review examines the current literature for the influence of the surgical timing in the setting of anterior cruciate ligament (ACL) reconstruction on various outcomes. Although the exact definition of early and delayed ACL reconstruction (ACLR) is a subject of controversy, surgical timing influences arthrofibrosis and postoperative stiffness, quadriceps strength, postoperative knee function, and the incidence of intra-articular injuries to the menisci and cartilage. Additionally, there is a shortage of evidence regarding the role of ACLR timing in the setting of multiligament knee injury and when concurrent procedures are performed during the operative treatment of the ACL-injured knee.
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Affiliation(s)
- Bálint Zsidai
- Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
| | - Janina Kaarre
- Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Orthopaedic Surgery, UPMC Freddie Fu Sports Medicine Center, University of Pittsburgh, 3200 South Water Street, Pittsburgh, PA, USA
| | - Eric Narup
- Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Kristian Samuelsson
- Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Orthopaedics, Sahlgrenska University Hospital, Göteborgsvägen 31, 431 30 Mölndal, Sweden
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Tseng TH, Chen CL, Chang CH, Wang JH, Young TH. IL-6 induces periostin production in human ACL remnants: a possible mechanism causing post-traumatic osteoarthritis. J Orthop Surg Res 2023; 18:824. [PMID: 37919719 PMCID: PMC10621128 DOI: 10.1186/s13018-023-04308-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 10/22/2023] [Indexed: 11/04/2023] Open
Abstract
OBJECTIVE Perostin (POSTN) and IL-6 consistently elevated after ACL injury, and ACL has been proposed as the major source of POSTN. However, there is a lack of evidence whether IL-6 induces ACL remnants to produce POSTN. This study aimed to investigate the effect of IL-6 on POSTN production in ACL fibroblasts, which may help us understand more about the mechanism of PTOA after ACL injury and ACL reconstruction. METHODS ACL remnants were harvested from 27 patients undergoing ACL reconstruction. Quantitative real-time polymerase chain reaction (PCR) was performed to examine the POSTN gene expression of ACL fibroblasts after treatment of different concentrations of IL-6. The POSTN protein production of ACL fibroblasts was determined using western blot analysis. The blockers of possible signaling pathways, including PI3K/Akt, Ras/MAPK, and JAK/STAT pathways, were added to test whether the effect of IL-6 on ACL fibroblast could be attenuated. ACL fibroblast and chondrocyte co-culture was carried out to determine the influence of ACL and IL-6 on chondrocytes. RESULTS Quantitative real-time PCR showed that IL-6 time-dependently and dose-dependently increased POSTN gene expression of ACL fibroblast. Western blot analysis also revealed that IL-6 dose-dependently induced POSTN protein production. Regarding the chronicity of ACL injury, the POSTN protein production was comparable between ACL remnants which were derived within 3 months of injury and at least 6 months after injury. PI3K/Akt blockers could attenuate the effect of IL-6 on ACL remnants, whereas Ras/MAPK and JAK/STAT did not decrease POSTN production. The coexistence of ACL and IL-6 induced more MMP-13 and ADAMTS-4 by chondrocytes. CONCLUSIONS IL-6 induced ACL remnants to produce POSTN. This effect could be attenuated by the PI3K/Akt blocker. Coexistence of IL-6 and ACL remnants may accelerate post-traumatic arthritis.
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Affiliation(s)
- Tzu-Hao Tseng
- Department of Biomedical Engineering, College of Medicine, National Taiwan University, No.1 Jen Ai Road Section 1, Taipei City, 10002, Taiwan
- Department of Orthopaedic Surgery, National Taiwan University Hospital, 7 Chungsan South Road, Taipei City, 10002, Taiwan
| | - Chien-Lin Chen
- Department of Biomedical Engineering, College of Medicine, National Taiwan University, No.1 Jen Ai Road Section 1, Taipei City, 10002, Taiwan
| | - Chung-Hsun Chang
- Department of Orthopaedic Surgery, National Taiwan University Hospital, 7 Chungsan South Road, Taipei City, 10002, Taiwan
| | - Jyh-Horng Wang
- Department of Orthopaedic Surgery, National Taiwan University Hospital, 7 Chungsan South Road, Taipei City, 10002, Taiwan.
| | - Tai-Horng Young
- Department of Biomedical Engineering, College of Medicine, National Taiwan University, No.1 Jen Ai Road Section 1, Taipei City, 10002, Taiwan.
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Turati M, Franchi S, Crippa M, Rizzi L, Rigamonti L, Sacerdote P, Gatti SD, Piatti M, Galimberti G, Munegato D, Amodeo G, Omeljaniuk RJ, Zatti G, Torsello A, Bigoni M. Prokineticin 2 and Cytokine Content in the Synovial Fluid of Knee Osteoarthritis and Traumatic Meniscal Tear Patients: Preliminary Results. J Clin Med 2023; 12:4330. [PMID: 37445367 DOI: 10.3390/jcm12134330] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 06/15/2023] [Accepted: 06/24/2023] [Indexed: 07/15/2023] Open
Abstract
Knee osteoarthritis (OA) is a chronic degenerative inflammatory-based condition caused by a cascade of different intra-articular molecules including several cytokines. Among the cytokines, prokineticins (PKs) have recently been identified as important mediators of inflammation and pain. This observational study examined the potential involvement of PK2 in degenerative or traumatic knee disease. Fifteen patients presenting knee osteoarthritis (OA group) and 15 patients presenting a traumatic meniscal tear (TM group) were studied. Synovial fluid samples from affected knees were assessed for PK2, IL-10, and TNF-α using the ELISA method. At a long-term follow-up (minimum 5 years, mean = 6.1 years), patients in the TM group underwent clinical re-evaluation with PROMs (Tegner Activity Scale, IKDC, Lysholm, SKV); in addition, X-ray visualization was used to assess the presence of secondary OA. PK2 was detected in synovial fluids of both TM and OA patients and the levels were comparable between the two groups, while IL-10 levels were significantly greater in the OA group than those in TM patients. PK2 levels correlated with those of IL-10. PK2 levels were greater in blood effusions compared to clear samples, did not differ significantly between sexes, nor were they related to differences in weight, height, or injury (meniscal laterality, time since dosing). No correlation was found between PROMs and radiological classifications in patients in the TM group at final follow-up. These data are the first observations of PK2 in synovial fluid following traumatic meniscus injury. These findings suggest possible further prognostic indices and therapeutic targets to limit the development of secondary OA.
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Affiliation(s)
- Marco Turati
- Orthopedic Department, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Department of Paediatric Orthopedic Surgery, Hospital Couple Enfants, Grenoble Alpes University, 38400 Grenoble, France
| | - Silvia Franchi
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20129 Milan, Italy
| | - Marco Crippa
- Orthopedic Department, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
| | - Laura Rizzi
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
| | - Luca Rigamonti
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Department of Orthopedic Surgery, Policlinico San Pietro, 24036 Ponte San Pietro, Italy
| | - Paola Sacerdote
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20129 Milan, Italy
| | - Simone Daniel Gatti
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
| | - Massimiliano Piatti
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Department of Orthopedic Surgery, Policlinico San Pietro, 24036 Ponte San Pietro, Italy
| | - Giulia Galimberti
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20129 Milan, Italy
| | - Daniele Munegato
- Orthopedic Department, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
| | - Giada Amodeo
- Department of Pharmacological and Biomolecular Sciences, University of Milan, 20129 Milan, Italy
| | | | - Giovanni Zatti
- Orthopedic Department, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
| | - Antonio Torsello
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
| | - Marco Bigoni
- School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Department of Orthopedic Surgery, Policlinico San Pietro, 24036 Ponte San Pietro, Italy
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Anterior Screw Insertion Results in Greater Tibial Tunnel Enlargement Rates after Single-Bundle Anterior Cruciate Ligament Reconstruction than Posterior Insertion: A Retrospective Study. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020390. [PMID: 36837591 PMCID: PMC9967347 DOI: 10.3390/medicina59020390] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/11/2023] [Accepted: 02/16/2023] [Indexed: 02/19/2023]
Abstract
Background and Objectives: Tunnel enlargement (TE) is a widely reported phenomenon after anterior cruciate ligament reconstruction (ACLR). Given the paucity of knowledge in the literature, it remains unclear whether screw position in the tunnel affects TE. This retrospective cohort study evaluated differences in postoperative tunnel enlargement rates (TER) and clinical results between anterior and posterior tibial interference screw insertion during single-bundle ACLR using autologous hamstring grafts. Materials and Methods: A group of consecutive patients that underwent primary arthroscopic single-bundle ACLR in our hospital were screened and divided into two groups based on the position of the tibial interference screw (determined by Computer Tomography within 3 days after surgery): anterior screw position group (A) and posterior screw position group (B). The bone tunnel size was measured using magnetic resonance imaging (MRI) performed 1 year after surgery. International Knee Documentation Committee (IKDC) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were used for clinical results 1 year postoperatively. Results: 87 patients were included. The TER of Group A is higher than that of Group B (43.17% vs. 33.80%, p = 0.024). Group A showed a significant increase (12.1%) in enlargement rates at the joint line level than group B (43.77% vs. 31.67%, p = 0.004). Moreover, KOOS and IKDC scores improved in both groups. There were no significant differences in clinical outcomes between the two groups. Conclusions: One year after ACLR, patients with posterior screw showed significantly lower TE than patients with anterior screw. However, the position of screw did not lead to differences in clinical results over our follow-up period. Posterior screw position in the tibial tunnel maybe a better choice in terms of reducing TE. Whether the different screw positions affect the long-term TE and long-term clinical outcomes needs to be confirmed by further studies.
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Return to sport soccer after anterior cruciate ligament reconstruction: ISAKOS consensus. J ISAKOS 2022; 7:150-161. [PMID: 35998884 DOI: 10.1016/j.jisako.2022.08.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 08/07/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Many factors can affect the return to pivoting sports, after an Anterior Cruciate Ligament Reconstruction. Prehabilitation, rehabilitation, surgical and psychological aspects play an essential role in the decision to return to sports. The purpose of this study is to reach an international consensus about the best conditions for returning to sports in soccer-one of the most demanding level I pivoting sports after anterior cruciate ligament (ACL) reconstruction. METHODS 34 International experts in the management of ACL injuries, representing all the Continents were convened and participated in a process based on the Delphi method to achieve a consensus. 37 statements related to ACL reconstruction were reviewed by the experts in three rounds of surveys in complete anonymity. The statements were prepared by the working group based on previous literature or systematic reviews. Rating agreement through a Likert Scale: strongly agree, agree, neither agree or disagree, disagree and strongly disagree was used. To define consensus, it was established that the assertions should achieve a 75% of agreement or disagreement. RESULTS Of the 37 statements, 10 achieved unanimous consensus, 18 non-unanimous consensus and 9 did not achieve consensus. In the preoperative, the correction of the range of motion deficit, the previous high level of participation in sports and a better knowledge of the injury by the patient and compliance to participate in Rehabilitation were the statements that reached unanimous consensus. During the surgery, the treatment of associated injuries, as well as the use of autografts, and the addition of a lateral extra-articular tenodesis in some particular cases (active young athletes, <25 years old, hyperlaxity, high rotatory laxity and revision cases) obtained also 100% consensus. In the postoperative period, psychological readiness and its validation with scales, adequate physical preparation, as well as not basing the RTSS purely on the time of evolution after surgery, were the factors that reached unanimous Consensus. CONCLUSIONS The consensus statements derived from this international ISAKOS leaders, may assist clinicians in deciding when to return to sports soccer in patients after an ACL reconstruction. Those statements that reached 100% consensus have to be strongly considered in the final decision to RTS soccer.
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Campón Chekroun A, Velázquez-Saornil J, Guillén Vicente I, Sánchez Milá Z, Rodríguez-Sanz D, Romero-Morales C, Fernandez-Jaén T, Garrido González JI, Sánchez-Garrido MÁ, Guillén García P. Consensus Delphi study on guidelines for the assessment of anterior cruciate ligament injuries in children. World J Orthop 2022; 13:777-790. [PMID: 36189335 PMCID: PMC9516626 DOI: 10.5312/wjo.v13.i9.777] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/16/2022] [Accepted: 08/17/2022] [Indexed: 02/06/2023] Open
Abstract
Background: Knee examination guidelines in minors are intended to aid decision-making in the management of knee instability. Clinical question: A Delphi study was conducted with a formal consensus process using a validated methodology with sufficient scientific evidence. A group consensus meeting was held to develop recommendations and practical guidelines for use in the assessment of instability injuries in children. Key findings: there is a lack of evidence to analyse anterior cruciate ligament injuries in children and their subsequent surgical management if necessary. Diagnostic guidelines and clinical assessment of the patient based on a thorough examination of the knee are performed and a guide to anterior cruciate ligament exploration in children is developed. Clinical application: In the absence of a strong evidence base, these established guidelines are intended to assist in that decision-making process to help the clinician decide on the most optimal treatment with the aim of benefiting the patient as much as possible. Following this expert consensus, surgical treatment is advised when the patient has a subjective sensation of instability accompanied by a pivot shift test ++, and may include an anterior drawer test + and a Lachman test +. If these conditions are not present, the conservative approach should be chosen, as the anatomical and functional development of children, together with a physiotherapy programme, may improve the evolution of the injury.
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Affiliation(s)
| | | | - Isabel Guillén Vicente
- Department of Orthopaedic and Trauma Surgery, Clínica Cemtro, Madrid 28035, Madrid, Spain
| | - Zacarías Sánchez Milá
- Department of Physiotherapy, Universidad Católica de Ávila, Ávila 05005, Ávila, Spain
| | - David Rodríguez-Sanz
- Nursing, Physiotherapy and Podiatry, Universidad Complutense de Madrid, Madrid 28040, Madrid, Spain
| | - Carlos Romero-Morales
- Department of Physical Therapy, Universidad Europea de Madrid, Madrid 28023, Madrid, Spain
| | - Tomas Fernandez-Jaén
- Department of Orthopaedic and Trauma Surgery, Clínica Cemtro, Madrid 28035, Madrid, Spain
| | | | | | - Pedro Guillén García
- Department of Orthopaedic and Trauma Surgery, Clínica Cemtro, Madrid 28035, Madrid, Spain
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Orozco GA, Eskelinen AS, Kosonen JP, Tanaka MS, Yang M, Link TM, Ma B, Li X, Grodzinsky AJ, Korhonen RK, Tanska P. Shear strain and inflammation-induced fixed charge density loss in the knee joint cartilage following ACL injury and reconstruction: A computational study. J Orthop Res 2022; 40:1505-1522. [PMID: 34533840 PMCID: PMC8926939 DOI: 10.1002/jor.25177] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 07/13/2021] [Accepted: 09/01/2021] [Indexed: 02/04/2023]
Abstract
Excessive tissue deformation near cartilage lesions and acute inflammation within the knee joint after anterior cruciate ligament (ACL) rupture and reconstruction surgery accelerate the loss of fixed charge density (FCD) and subsequent cartilage tissue degeneration. Here, we show how biomechanical and biochemical degradation pathways can predict FCD loss using a patient-specific finite element model of an ACL reconstructed knee joint exhibiting a chondral lesion. Biomechanical degradation was based on the excessive maximum shear strains that may result in cell apoptosis, while biochemical degradation was driven by the diffusion of pro-inflammatory cytokines. We found that the biomechanical model was able to predict substantial localized FCD loss near the lesion and on the medial areas of the lateral tibial cartilage. In turn, the biochemical model predicted FCD loss all around the lesion and at intact areas; the highest FCD loss was at the cartilage-synovial fluid-interface and decreased toward the deeper zones. Interestingly, simulating a downturn of an acute inflammatory response by reducing the cytokine concentration exponentially over time in synovial fluid led to a partial recovery of FCD content in the cartilage. Our novel numerical approach suggests that in vivo FCD loss can be estimated in injured cartilage following ACL injury and reconstruction. Our novel modeling platform can benefit the prediction of PTOA progression and the development of treatment interventions such as disease-modifying drug testing and rehabilitation strategies.
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Affiliation(s)
- Gustavo A. Orozco
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland Yliopistonranta 1, FI-70210 Kuopio, Finland,Department of Biomedical Engineering, Lund University, Box 188, 221 00, Lund, Sweden
| | - Atte S.A. Eskelinen
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland Yliopistonranta 1, FI-70210 Kuopio, Finland
| | - Joonas P. Kosonen
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland Yliopistonranta 1, FI-70210 Kuopio, Finland
| | - Matthew S. Tanaka
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, 1500 Owens St, San Francisco, CA 94158, USA
| | - Mingrui Yang
- Department of Biomedical Engineering, Lerner Research Institute, Program of Advanced Musculoskeletal Imaging (PAMI), 9500 Euclid Avenue, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Thomas M. Link
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, 1500 Owens St, San Francisco, CA 94158, USA
| | - Benjamin Ma
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, 1500 Owens St, San Francisco, CA 94158, USA
| | - Xiaojuan Li
- Department of Biomedical Engineering, Lerner Research Institute, Program of Advanced Musculoskeletal Imaging (PAMI), 9500 Euclid Avenue, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Alan J. Grodzinsky
- Departments of Biological Engineering, Electrical Engineering and Computer Science and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Rami K. Korhonen
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland Yliopistonranta 1, FI-70210 Kuopio, Finland
| | - Petri Tanska
- Department of Applied Physics, University of Eastern Finland, Kuopio, Finland Yliopistonranta 1, FI-70210 Kuopio, Finland
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de Melo Viveiros ME, Viveiros MMH, da Silva MG, Rainho CA, Schellini SA. In vitro effect of triamcinolone and platelet-rich plasma on cytokine levels of elbow lateral epicondylitis-derived cells. J Orthop Surg Res 2022; 17:94. [PMID: 35168647 PMCID: PMC8848654 DOI: 10.1186/s13018-022-02990-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 02/03/2022] [Indexed: 12/04/2022] Open
Abstract
Background The pathogenesis and treatment of lateral elbow epicondylitis (LEE) are still controversial. The purpose of the current study was to evaluate the production of inflammatory cytokines by LEE-derived cells and to compare the anti-inflammatory effect of triamcinolone acetonide with platelet-rich plasma (PRP) on cytokines production in primary culture of these cells.
Methods Third passage cells from primary cultures of LEE were assessed for the production of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α by immune-enzymatic assay (ELISA), after the treatment with 1, 10 and 100 μM triamcinolone compared to no treated controls at the time points 6, 12, 18, 24, 48, 72 and 96 h, and to PRP at 48, 72 and 96 h. Results The cytokines IL-6 and IL-8 were produced in high concentrations by LEE cells. One, 10 and 100 μM triamcinolone induced significant decrease in the production of IL-6 and IL-8 at 48, 72 and 96 h, adding the time point 12 h for IL-8. Compared to controls, PRP caused a significant increase in the production of IL-6 and IL-8 and there was a significant increase in IL-10 production with the use of 100 μM triamcinolone at 48 h. The production of IL1-β and TNF-α was very low and did not change when the cultures were treated with triamcinolone or PRP. Conclusion LEE-derived cells produce IL-6 and IL-8, confirming the inflammatory nature of this condition. While triamcinolone inhibited the production of IL-6 and IL-8 by LEE cells, PRP induced an increase in these cytokines compared with controls. Supplementary Information The online version contains supplementary material available at 10.1186/s13018-022-02990-0.
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Affiliation(s)
- Márcio Eduardo de Melo Viveiros
- Department of Orthopedics and Traumatology, School of Medicine of Botucatu, São Paulo State University - UNESP, Botucatu, SP, Brazil
| | - Magda Massae Hata Viveiros
- Department of Ophthalmology, School of Medicine of Botucatu, São Paulo State University - UNESP, Botucatu, SP, 18618-970, Brazil
| | - Márcia Guimarães da Silva
- Department of Pathology, School of Medicine of Botucatu, São Paulo State University - UNESP, Botucatu, SP, Brazil
| | - Cláudia Aparecida Rainho
- Department of Chemical and Biological Sciences, Institute of Biosciences of Botucatu, São Paulo State University - UNESP, Botucatu, SP, Brazil
| | - Silvana Artioli Schellini
- Department of Ophthalmology, School of Medicine of Botucatu, São Paulo State University - UNESP, Botucatu, SP, 18618-970, Brazil.
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Kingery MT, Anil U, Berlinberg EJ, Clair AJ, Kenny L, Strauss EJ. Changes in the Synovial Fluid Cytokine Profile of the Knee Between an Acute Anterior Cruciate Ligament Injury and Surgical Reconstruction. Am J Sports Med 2022; 50:451-460. [PMID: 35049392 DOI: 10.1177/03635465211062264] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Changes in the intra-articular inflammatory state during the immediate period after an acute anterior cruciate ligament (ACL) rupture are not well defined. PURPOSE To evaluate changes in the concentration of select proinflammatory and anti-inflammatory synovial fluid cytokines during the interval between an ACL injury and surgical reconstruction. STUDY DESIGN Descriptive laboratory study. METHODS In patients with an acute ACL injury, a synovial fluid sample was obtained from the injured knee during the initial office visit within 2 weeks of the inciting traumatic event. An additional synovial fluid sample was collected at the time of ACL reconstruction just before the surgical incision. Synovial fluid samples from both the acute injury and the surgery time points were processed with a protease inhibitor, and the concentrations of 10 cytokines of interest were measured using a multiplex magnetic bead immunoassay. The primary outcome was the change in cytokine concentrations between time points. RESULTS A total of 20 patients with a mean age of 30.2 ± 8.3 years were included. The acute injury synovial fluid samples were collected at 6.6 ± 3.8 days after the injury. The surgical synovial fluid samples were collected at 31.6 ± 15.6 days after the acute injury samples. Based on a series of linear mixed-effects models to control for the effect of concomitant meniscal injuries and by-patient variability, there was a statistically significant increase in the concentrations of RANTES and bFGF and a statistically significant decrease in the concentrations of IL-6, MCP-1, MIP-1β, TIMP-1, IL-1Ra, and VEGF between time points. CONCLUSION This study demonstrates the ongoing alterations in the intra-articular microenvironment during the initial inflammatory response in the acute postinjury period. We identified 6 synovial fluid cytokines that significantly decreased and 2 that significantly increased between the first clinical presentation shortly after the injury and the time of surgery 1 month later. CLINICAL RELEVANCE This study describes the molecular profile of the inflammatory changes between the time of an acute ACL injury and the time of surgical reconstruction 1 month later. A greater understanding of the acute inflammatory response within the knee may be helpful in identifying the optimal timing for a surgical intervention that balances the risk of chondral damage with the likelihood of successful, well-healed reconstruction.
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Affiliation(s)
- Matthew T Kingery
- Division of Sports Medicine, Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, New York, USA
| | - Utkarsh Anil
- Division of Sports Medicine, Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, New York, USA
| | - Elyse J Berlinberg
- Division of Sports Medicine, Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, New York, USA
| | - Andrew J Clair
- Division of Sports Medicine, Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, New York, USA
| | - Lena Kenny
- Division of Sports Medicine, Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, New York, USA
| | - Eric J Strauss
- Division of Sports Medicine, Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, New York, USA
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Davi SM, Ahn A, White MS, Butterfield TA, Kosmac K, Kwon OS, Lepley LK. Long-Lasting Impairments in Quadriceps Mitochondrial Health, Muscle Size, and Phenotypic Composition Are Present After Non-invasive Anterior Cruciate Ligament Injury. Front Physiol 2022; 13:805213. [PMID: 35153832 PMCID: PMC8832056 DOI: 10.3389/fphys.2022.805213] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 01/03/2022] [Indexed: 11/13/2022] Open
Abstract
IntroductionDespite rigorous rehabilitation aimed at restoring muscle health, anterior cruciate ligament (ACL) injury is often hallmarked by significant long-term quadriceps muscle weakness. Derangements in mitochondrial function are a common feature of various atrophying conditions, yet it is unclear to what extent mitochondria are involved in the detrimental sequela of quadriceps dysfunction after ACL injury. Using a preclinical, non-invasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on mitochondrial function, muscle atrophy, and muscle phenotypic transitions.MethodsA total of 40 male and female, Long Evans rats (16-week-old) were exposed to non-invasive ACL injury, while 8 additional rats served as controls. Rats were euthanized at 3, 7, 14, 28, and 56 days after ACL injury, and vastus lateralis muscles were extracted to measure the mitochondrial respiratory control ratio (RCR; state 3 respiration/state 4 respiration), mitochondrial reactive oxygen species (ROS) production, fiber cross sectional area (CSA), and fiber phenotyping. Alterations in mitochondrial function and ROS production were detected using two-way (sex:group) analyses of variance. To determine if mitochondrial characteristics were related to fiber atrophy, individual linear mixed effect models were run by sex.ResultsMitochondria-derived ROS increased from days 7 to 56 after ACL injury (30–100%, P < 0.05), concomitant with a twofold reduction in RCR (P < 0.05). Post-injury, male rats displayed decreases in fiber CSA (days 7, 14, 56; P < 0.05), loss of IIa fibers (day 7; P < 0.05), and an increase in IIb fibers (day 7; P < 0.05), while females displayed no changes in CSA or phenotyping (P > 0.05). Males displayed a positive relationship between state 3 respiration and CSA at days 14 and 56 (P < 0.05), while females only displayed a similar trend at day 14 (P = 0.05).ConclusionLong-lasting impairments in quadriceps mitochondrial health are present after ACL injury and play a key role in the dysregulation of quadriceps muscle size and composition. Our preclinical data indicate that using mitoprotective therapies may be a potential therapeutic strategy to mitigate alterations in muscle size and characteristic after ACL injury.
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Affiliation(s)
- Steven M. Davi
- Department of Kinesiology, University of Connecticut, Storrs, CT, United States
- Department of Orthopedic Surgery, John A. Feagin Jr Sports Medicine Fellowship, Keller Army Hospital, West Point, NY, United States
| | - Ahram Ahn
- Department of Kinesiology, University of Connecticut, Storrs, CT, United States
| | - McKenzie S. White
- School of Kinesiology, University of Michigan, Ann Arbor, MI, United States
| | - Timothy A. Butterfield
- Center for Muscle Biology, University of Kentucky, Lexington, KY, United States
- Department of Athletic Training and Clinical Nutrition, University of Kentucky, Lexington, KY, United States
| | - Kate Kosmac
- Center for Muscle Biology, University of Kentucky, Lexington, KY, United States
- Department of Physical Therapy, University of Kentucky, Lexington, KY, United States
| | - Oh Sung Kwon
- Department of Kinesiology, University of Connecticut, Storrs, CT, United States
- Department of Orthopaedic Surgery and Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States
- *Correspondence: Oh Sung Kwon,
| | - Lindsey K. Lepley
- School of Kinesiology, University of Michigan, Ann Arbor, MI, United States
- Lindsey K. Lepley,
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Williams AA, Deadwiler BC, Dragoo JL, Chu CR. Cartilage Matrix Degeneration Occurs within the First Year after ACLR and Is Associated with Impaired Clinical Outcome. Cartilage 2021; 13:1809S-1818S. [PMID: 34894770 PMCID: PMC8804799 DOI: 10.1177/19476035211063856] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 11/02/2021] [Accepted: 11/02/2021] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE Anterior cruciate ligament reconstruction (ACLR) has not been shown to decrease the risk for development of post-traumatic osteoarthritis. Magnetic resonance imaging (MRI) T2 mapping can be used to assess cartilage compositional changes. This study tests whether (1) worse cartilage arthroscopic status at ACLR is reflected by higher cartilage T2 values in matched study regions 6 weeks and 1 year after ACLR, and (2) increasing cartilage T2 values between 6 weeks and 1 year after ACLR are associated with worsening patient-reported outcomes. DESIGN Twenty-two participants with ACLR and 26 controls underwent 3T MRI. T2 values in medial and lateral femoral and tibial cartilage were measured at 6 weeks and 1 year after ACLR and compared with arthroscopic grades, Knee injury and Osteoarthritis Outcome Scores (KOOS), and control T2 values. RESULTS Most (59%-86%) cartilage study regions examined by arthroscopy demonstrated intact articular surfaces. Average T2 value increased in 3 of 4 study regions between 6 weeks and 1 year after ACLR (P = .001-.011). T2 value increased (P < .013) even for participants whose cartilage had intact articular surfaces at ACLR. Participants with ACLR who showed greater increases in cartilage T2 values had less improvement to KOOS Quality of Life (P = .009, ρ = -0.62). DISCUSSION Cartilage status assessed arthroscopically at ACLR and by MRI T2 maps 6 weeks later was healthier than cartilage status assessed by MRI T2 maps at 1-year follow-up. Progressive T2 elevations were observed over the first year after ACLR even in patients with arthroscopically intact cartilage at the time of surgery and were associated with reduced improvement in knee quality of life suggesting preosteoarthritis.
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Affiliation(s)
- Ashley A. Williams
- Department of Orthopaedic Surgery,
Stanford University, Stanford, CA, USA
- Veterans Affairs Palo Alto Healthcare
System, Palo Alto, CA, USA
| | | | - Jason L. Dragoo
- Department of Orthopaedics, University
of Colorado, Denver, CO, USA
| | - Constance R. Chu
- Department of Orthopaedic Surgery,
Stanford University, Stanford, CA, USA
- Veterans Affairs Palo Alto Healthcare
System, Palo Alto, CA, USA
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16
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Turati M, Franchi S, Leone G, Piatti M, Zanchi N, Gandolla M, Rigamonti L, Sacerdote P, Rizzi L, Pedrocchi A, Omeljaniuk RJ, Zatti G, Torsello A, Bigoni M. Resolvin E1 and Cytokines Environment in Skeletally Immature and Adult ACL Tears. Front Med (Lausanne) 2021; 8:610866. [PMID: 34150787 PMCID: PMC8208028 DOI: 10.3389/fmed.2021.610866] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 04/22/2021] [Indexed: 01/25/2023] Open
Abstract
The intra-articular synovial fluid environment in skeletally immature patients following an ACL tear is complex and remains undefined. Levels of inflammatory and anti-inflammatory cytokines change significantly in response to trauma and collectively define the inflammatory environment. Of these factors the resolvins, with their inherent anti-inflammatory, reparative, and analgesic properties, have become prominent. This study examined the levels of resolvins and other cytokines after ACL tears in skeletally immature and adult patients in order to determine if skeletal maturity affects the inflammatory pattern. Skeletally immature and adult patients with an anterior cruciate ligament injury and meniscal tears were prospectively enrolled over a 5-month period. Synovial fluid samples were obtained before surgery quantifying Resolvin E1, IL-1β, TNF-α, and IL-10 by ELISA. Comparisons between skeletally immature patients and adults, the influence of meniscal tear, growth plate maturity and time from trauma were analyzed. Skeletally immature patients had significantly greater levels of Resolvin E1 and IL-10 compared with adults with an isolated anterior cruciate ligament lesion. Among the injured skeletally immature patients Resolvin E1 levels were greater in the open growth plate group compared with those with closing growth plates. Moreover, levels of Resolvin E1 and IL-10 appeared to decrease with time. Our results suggest that skeletally immature patients have a stronger activation of the Resolvin pattern compared to adult patients and that synovial fluid Resolvins could play an antinflammatory role in the knee after anterior cruciate ligament lesion and that its activity may be synergistic with that of IL-10.
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Affiliation(s)
- Marco Turati
- Orthopedic Department, San Gerardo Hospital, Monza, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Grenoble, France
- Department of Pediatric Orthopedic Surgery, Hopital Couple Enfants, Grenoble Alpes University, Grenoble, France
| | - Silvia Franchi
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Giulio Leone
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Grenoble, France
| | - Massimiliano Piatti
- Orthopedic Department, San Gerardo Hospital, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Grenoble, France
| | - Nicolò Zanchi
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Grenoble, France
| | - Marta Gandolla
- NearLab, Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy
| | - Luca Rigamonti
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, United States
| | - Paola Sacerdote
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Laura Rizzi
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Alessandra Pedrocchi
- NearLab, Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy
| | | | - Giovanni Zatti
- Orthopedic Department, San Gerardo Hospital, Monza, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Grenoble, France
| | - Antonio Torsello
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Marco Bigoni
- Orthopedic Department, San Gerardo Hospital, Monza, Italy
- School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Monza, Italy
- Transalpine Center of Pediatric Sports Medicine and Surgery, University of Milano-Bicocca - Hospital Couple Enfant, Grenoble, France
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Hunt ER, Jacobs CA, Conley CEW, Ireland ML, Johnson DL, Lattermann C. Anterior cruciate ligament reconstruction reinitiates an inflammatory and chondrodegenerative process in the knee joint. J Orthop Res 2021; 39:1281-1288. [PMID: 32558951 DOI: 10.1002/jor.24783] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 06/04/2020] [Accepted: 06/12/2020] [Indexed: 02/04/2023]
Abstract
Anterior cruciate ligament (ACL) injury leads to a sustained increase in synovial fluid concentrations of inflammatory cytokines and biomarkers of cartilage breakdown. While this has been documented post-injury, it remains unclear whether ACL reconstruction surgery contributes to the inflammatory process and/or cartilage breakdown. This study is a secondary analysis of 14 patients (nine males/five females, mean age = 9, mean BMI = 28) enrolled in an IRB-approved randomized clinical trial. Arthrocentesis was performed at initial presentation (mean = 6 days post-injury), immediately prior to surgery (mean = 23 days post-injury), 1-week post-surgery, and 1-month post-surgery. Enzyme-linked immunosorbant assay kits were used to determine concentrations of carboxy-terminal telopeptides of type II collagen (CTXII), interleukin-6 (IL-6), and IL-1β in the synovial fluid. The log-transformed IL-1β was not normally distributed; therefore, changes between time points were evaluated using a non-parametric Kruskal-Wallis one-way ANOVA. IL-1β concentrations significantly increased from the day of surgery to the first postoperative time point (P ≤ .001) and significantly decreased at the 4-week postoperative visit (P = .03). IL-1β concentrations at the 4-week postoperative visit remained significantly greater than both preoperative time points (P > .05). IL-6 concentrations at 1-week post-surgery were significantly higher than at initial presentation (P = .013), the day of surgery (P < .001), and 4 weeks after surgery (P = .002). CTX-II concentrations did not differ between the first three-time points (P > .99) but significantly increased at 4 weeks post-surgery (P < .01). ACL reconstruction appears to reinitiate an inflammatory response followed by an increase in markers for cartilage degradation. ACL reconstruction appears to initiate a second "inflammatory hit" resulting in increased chondral breakdown suggesting that post-operative chondroprotection may be needed.
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Affiliation(s)
- Emily R Hunt
- Department of Orthopedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky
| | - Cale A Jacobs
- Department of Orthopedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky
| | - Caitlin E-W Conley
- Department of Orthopedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky
| | - Mary L Ireland
- Department of Orthopedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky
| | - Darren L Johnson
- Department of Orthopedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky
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Characterization of Synovial Cytokine Patterns in Bucket-Handle and Posterior Horn Meniscal Tears. Mediators Inflamm 2020; 2020:5071934. [PMID: 33144846 PMCID: PMC7599409 DOI: 10.1155/2020/5071934] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 09/23/2020] [Accepted: 10/15/2020] [Indexed: 01/30/2023] Open
Abstract
The specific etiology of meniscal tears, including the mechanism of lesion, location, and orientation, is considered for its contribution to subsequent joint cytokine responsiveness, healing outcomes, and by extension, appropriate lesion-specific surgical remediation. Meniscal repair is desirable to reduce the probability of development of posttraumatic osteoarthritis (PTOA) which is strongly influenced by the coordinate generation of pro- and anti-inflammatory cytokines by the injured cartilage. We now present biochemical data on variation in cytokine levels arising from two particular meniscal tears: bucket-handle (BH) and posterior horn (PH) isolated meniscal tears. We selected these two groups due to the different clinical presentations. We measured the concentrations of TNF-α, IL-1β, IL-6, IL-8, and IL-10 in knee synovial fluid of 45 patients with isolated meniscal lesions (BH tear, n = 12; PH tear, n = 33). TNF-α levels were significantly (p < 0.05) greater in the BH group compared with the PH group, whereas IL-1β levels were significantly greater (p < 0.05) in the PH group compared with the BH group. Both BH and PH groups were consistent in presenting a positive correlation between concentrations of IL-6 and IL-1β. A fundamental difference in IL-10 responsiveness between the two groups was noted; specifically, levels of IL-10 were positively correlated with IL-6 in the BH group, whereas in the PH group, levels of IL-10 were positively correlated with IL-1β. Collectively, our data suggest a possible influence of the meniscal tear pattern to the articular cytokine responsiveness. This differential expression of inflammatory cytokines may influence the risk of developing PTOA in the long term.
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Chen C, Chen Y, Li M, Xiao H, Shi Q, Zhang T, Li X, Zhao C, Hu J, Lu H. Functional decellularized fibrocartilaginous matrix graft for rotator cuff enthesis regeneration: A novel technique to avoid in-vitro loading of cells. Biomaterials 2020; 250:119996. [PMID: 32334201 DOI: 10.1016/j.biomaterials.2020.119996] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 03/09/2020] [Accepted: 03/20/2020] [Indexed: 02/07/2023]
Abstract
Rapid and functional enthesis regeneration after rotator cuff tear (RCT) remains a challenge in clinic. Current tissue-engineering strategies for solving this challenge are focused on developing grafts with the mode of in-vitro loading cells on a scaffold. However, this mode is complicated and time-inefficient, moreover the preservation of this graft outside a cell incubator is highly inconvenient, thus limiting their clinical application. Developing a cell-free graft with chemotaxis to recruit postoperative injected cells may be a promising approach to solve these problems. Herein, we prepared a recombinant SDF-1α (termed as C-SDF-1α) capable of binding collagen and chemotaxis, which were then tethered on the collagen fibers of book-shaped decellularized fibrocartilage matrix (BDFM) to fabricate this cell-free graft (C-SDF-1α/BDFM). This C-SDF-1α/BDFM is noncytotoxicity and low-immunogenicity, allows synovium-derived mesenchymal stem cells (SMSCs) attachment and proliferation, and shows superior chondrogenic inducibility. More importantly, C-SDF-1α/BDFM released the tethered SDF-1α with a sustained release profile in-vitro and in-vivo, thus steadily recruiting chemokine (C-X-C motif) receptor 4 positive (CXCR4+) cells. Rats with RCT were repaired acutely with C-SDF-1α/BDFM together with postoperative CXCR4+SMSCs injection (C-SDF-1α/BDFM + CXCR4+SMSCs), BDFM in-vitro pre-loaded CXCR4+SMSCs (BDFM/CXCR4+SMSCs), or direct suture only (CTL). At postoperative 14-day, compared with BDFM/CXCR4+SMSCs, C-SDF-1α/BDFM + CXCR4+SMSCs showed a little more CXCR4+SMSCs at the healing site. At postoperative week 4 or 8, rats treated with C-SDF-1α/BDFM + CXCR4+SMSCs presented a similar RC healing quality as BDFM/CXCR4+SMSCs, both of which were significantly better than the CTL. Collectively, compared with conventional BDFM/CXCR4+SMSCs, C-SDF-1α/BDFM, as a cell-free graft with chemotaxis, could recruit postoperative injected CXCR4+cells into the healing site to participating RC healing, thus avoiding the complex process of in-vitro loading cells on a scaffold and necessitating immense care for the graft outside cell incubator, making it very convenient for clinical application.
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Affiliation(s)
- Can Chen
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Yang Chen
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Muzh Li
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Han Xiao
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Qiang Shi
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Tao Zhang
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Xing Li
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Chunfeng Zhao
- Division of Orthopedic Research and Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, 55905, United States
| | - Jianzhong Hu
- Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
| | - Hongbin Lu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China; Research Centre of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; Xiangya Hospital-International Chinese Musculeskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China; Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
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Li W, Li Z, Qie S, Li J, Xi JN, Gong WJ, Zhao Y, Chen XM. Biomechanical Evaluation of Preoperative Rehabilitation in Patients of Anterior Cruciate Ligament Injury. Orthop Surg 2020; 12:421-428. [PMID: 32147935 PMCID: PMC7189052 DOI: 10.1111/os.12607] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 11/17/2019] [Accepted: 12/11/2019] [Indexed: 02/06/2023] Open
Abstract
Objectives To investigate the biomechanical characteristics of patients with anterior cruciate ligament (ACL) injury by gait analysis, surface electromyography (SEMG), and proprioception test, and provide rehabilitation suggestions according to the results. Methods In this retrospective cohort study, 90 adults with unilateral ACL injury, ranging in age from 19 to 45 years (66 men and 24 women, average age: 30.03 ± 7.91) were recruited for this study form May 2018 to July 2019. They were divided into three groups according to the time after the injury: group A (3‐week to 1.5‐month), group B (1.5‐month to 1 year), and group C (more than 1 year). The SEMG signals were collected from the bilateral rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) and the root mean square (RMS) were used to assess muscular activity. SEMG were used to analyze muscles function, gait analysis was used to evaluate the walking stability, balance and location assessment were used to analyze the proprioception. Results Through the comparison between bilateral limbs, all muscles strength shown decreased (RF: 239.94 ± 129.70 vs 364.81 ± 148.98, P = 0.001; VM: 298.88 ± 175.41 vs 515.79 ± 272.49, P = 0.001; VL:389.54 ± 157.97 vs 594.28 ± 220.31, P < 0.001) and the division of proprioception became larger (tandem position: 7.79 ± 1.57 vs 6.33 ± 1.49, P = 0.001; stance with one foot: 8.13 ± 0.84 vs 7.1 ± 0.57, P = 0.003; variance of 30°: 6.96 ± 3.15 vs 4.45 ± 1.67, P = 0.03; variance of 60°: 4.64 ± 3.38 vs 2.75 ± 1.98, P = 0.044) in the injured side when compared to the non‐injured and 26 gait parameters were shown difference in group A. In group B, the muscle strength of VL shown decreased (VL: 381.23 ± 142.07 vs 603.9 ± 192.72, P < 0.001) and the division of location of 30° became larger (7.62 ± 4.98 vs 4.33 ± 3.24, P = 0.028) in the injured side when compared to the non‐injured side and there were eight gait parameters that showed differences. In group C, the muscle strength and proprioception showed no differences and only 16 gait parameters showed differences between the bilateral limbs. Conclusion The results proved the deterioration of proprioception in 30° of injured side will not recover and non‐injury side and will become worse after 1 year from the injury; among the VL, VM, and RF, the recovery rate of VL is the slowest and bilateral straight leg raising (SLR) (30°) is the best way to train it; the gait stability will be worse after 1 year from the injury. Therefore, we suggest that the training for proprioception in 30° and VL are important for the rehabilitation, and the ACL reconstruction should be performed within 1 year.
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Affiliation(s)
- Wei Li
- Department of Orthopedics, General Hospital of PLA, Beijing, China
| | - Zhongli Li
- Department of Orthopedics, General Hospital of PLA, Beijing, China
| | - Shuyan Qie
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Ji Li
- Department of Orthopedics, General Hospital of PLA, Beijing, China
| | - Jia-Ning Xi
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Wei-Jun Gong
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Yue Zhao
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Xue-Mei Chen
- Department of Health Management, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
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Morishita Y, Kanemura N, Kokubun T, Murata K, Takayanagi K. Acute molecular biological responses during spontaneous anterior cruciate ligament healing in a rat model. SPORT SCIENCES FOR HEALTH 2019. [DOI: 10.1007/s11332-019-00583-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Sun Y, Chen W, Hao Y, Gu X, Liu X, Cai J, Liu S, Chen J, Chen S. Stem Cell-Conditioned Medium Promotes Graft Remodeling of Midsubstance and Intratunnel Incorporation After Anterior Cruciate Ligament Reconstruction in a Rat Model. Am J Sports Med 2019; 47:2327-2337. [PMID: 31306585 DOI: 10.1177/0363546519859324] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Stem cell-conditioned medium (CM) has been increasingly used in regenerative medicine. However, its effect on graft-host integration after anterior cruciate ligament (ACL) reconstruction (ACLR) remains unclear. PURPOSE To examine the effect of human bone marrow stem cell (hBMSC)-CM on graft-bone integration and graft midsubstance ligamentization in a rat model of ACLR. STUDY DESIGN Controlled laboratory study. METHODS CM was obtained from the supernatant of commercially available hBMSCs in serum-free Dulbecco's modified Eagle medium (DMEM). In a rat model of an ACL injury, isometric ACLR was performed. Three groups were established: CM injection group (CM; n = 40), control injection group (CI; n = 40) with serum-free DMEM injections, and no injection group (NI; n = 40). An intra-articular injection was performed weekly. Micro-computed tomography was conducted at 2, 4, and 8 weeks postoperatively. Histological and biomechanical analyses were conducted at 4 and 8 weeks postoperatively. The NIH3T3 fibroblast was utilized as a model in vitro to examine the effect of CM using the cell counting kit-8 (CCK-8) assay and immunofluorescence staining of Ki-67, α-smooth muscle actin (α-SMA), and collagen 1 (Col 1). RESULTS At 4 and 8 weeks, the femoral and tibial bone tunnel areas as well as the interface between the graft and host bone were smaller, while the bone volume/total volume ratio was higher, in the CM group. Sharpey-like fibers formed at 8 weeks in the CM group. At 4 and 8 weeks, more Col 1 was noticed in the CM group than in the NI group (both P < .001) or CI group (both P < .001). Immunohistochemically, the α-SMA-positive area was up-regulated at the graft-bone interface at 4 weeks (P < .001) and declined at 8 weeks (P < .001) in the CM group compared with the other 2 groups. At the midsubstance, α-SMA expression decreased from 4 to 8 weeks in all groups and was significantly lower in the CM group than in the NI group (P < .01) or CI group (P < .05) at 8 weeks. The CCK-8 assay showed that CM increased NIH3T3 viability (P < .001) and the level of Ki-67 (P < .05), α-SMA (P < .001), and Col 1 (P < .001) in CM-educated NIH3T3 cells. CONCLUSION hBMSC-CM accelerates graft-bone incorporation and midsubstance ligamentization and enhances the proliferation, differentiation, and collagen synthesis of fibroblasts. CLINICAL RELEVANCE Graft-host integration is essential after ACLR. The current study identified a novel agent, that is, hBMSC-CM, as a candidate for promoting integration.
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Affiliation(s)
- Yaying Sun
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Wenbo Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yuefeng Hao
- Department of Orthopaedic Surgery, Northern Branch of Suzhou Municipal Hospital, Suzhou, China
| | - Xueping Gu
- Department of Orthopaedic Surgery, Northern Branch of Suzhou Municipal Hospital, Suzhou, China
| | - Xingwang Liu
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiangyu Cai
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Shaohua Liu
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiwu Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Shiyi Chen
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Silawal S, Willauschus M, Schulze-Tanzil G, Gögele C, Geßlein M, Schwarz S. IL-10 Could Play a Role in the Interrelation between Diabetes Mellitus and Osteoarthritis. Int J Mol Sci 2019; 20:ijms20030768. [PMID: 30759730 PMCID: PMC6387262 DOI: 10.3390/ijms20030768] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 01/19/2019] [Accepted: 01/31/2019] [Indexed: 12/11/2022] Open
Abstract
The association between osteoarthritis (OA), obesity and metabolic syndrome suggests an interrelation between OA and diabetes mellitus (DM). Little is known about the role of anti-inflammatory cytokine interleukin (IL)-10 in the interrelation between OA and DM. Hence, the effects of IL-10 under hyperglycemia (HG) and hyperinsulinemia (HI) in human articular chondrocytes (hAC) and chondrosarcoma cell line Okayama University Medical School (OUMS)-27 were examined. HAC and OUMS-27, cultured in normoglycemic (NG) and HG conditions were stimulated with insulin and/or IL-10. Cell survival, metabolic activity, proliferation and extracellular matrix (ECM) synthesis were immunocytochemically examined. No significant differences in vitality of hAC neither in pure NG (NGw/o) nor HG (HGw/o) conditions were found. Applying HI and/or IL-10 in both conditions reduced significantly the vitality of hAC but not of OUMS-27. HG impaired significantly hAC metabolism. When combined with HI + IL-10 or IL-10 alone it decreased also significantly hAC proliferation compared to NGw/o. In OUMS-27 it induced only a trend of impaired proliferation compared to NGw/o. hAC but not OUMS-27 reduced significantly their collagen type (col) I, SOX9 and proteoglycan (PG) synthesis in HG combined with HI +/− IL-10 compared to NGw/o. IL-10 could not moderate HI and HG effects. In contrast to hAC OUMS-27 showed limited sensitivity as DM model.
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Affiliation(s)
- Sandeep Silawal
- Institute of Anatomy, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany.
| | - Maximilian Willauschus
- Institute of Anatomy, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany.
| | - Gundula Schulze-Tanzil
- Institute of Anatomy, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany.
| | - Clemens Gögele
- Institute of Anatomy, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany.
- Department of Biosciences, Paris Lodron University Salzburg, Hellbrunnerstr. 34, 5020 Salzburg, Austria.
| | - Markus Geßlein
- Department of Orthopedics and Trauma Surgery, Nuremberg General Hospital, Paracelsus Medical University, Nueremberg. Breslauer Strasse 201, 90471 Nuremberg, Germany.
| | - Silke Schwarz
- Institute of Anatomy, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany.
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Proteasome Activity and C-Reactive Protein Concentration in the Course of Inflammatory Reaction in Relation to the Type of Abdominal Operation and the Surgical Technique Used. Mediators Inflamm 2018; 2018:2469098. [PMID: 30405319 PMCID: PMC6204193 DOI: 10.1155/2018/2469098] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 09/04/2018] [Accepted: 09/10/2018] [Indexed: 11/30/2022] Open
Abstract
Surgical tissue damage and the accompanying inflammatory response lead to proteasome activation, initiation of damaged protein degradation, and induction of acute-phase inflammatory response. The aim of this study was to investigate the rate of change in proteasome chymotrypsin-like (ChT-L) activity and C-reactive protein concentration depending on the degree of tissue damage and their correlation with prealbumin concentrations in children before and after abdominal surgery. This experimental study included children who underwent abdominal surgery between 2015 and 2017. Plasma prealbumin concentrations and C-reactive protein levels (CRP) were determined by standard biochemical laboratory procedures. Proteasome activity was assessed using a Suc-Leu-Leu-Val-Tyr-AMC peptide substrate. Elevation of plasma proteasome activity was noted in children after laparoscopic and open abdominal surgeries. However, 20S proteasome activity in children undergoing conventional open surgery was significantly higher (P < 0.05) than in patients subjected to laparoscopy. At the same time, an increase in the CRP level was observed. However, there was no correlation between C-reactive protein concentrations and the type of abdominal surgery while there was a correlation observed in the case of proteasomes. Proteasome activity correlates with the degree of surgical tissue damage and prealbumin concentrations. More invasive surgery leads to a stronger activation of the proteasome involved in removing proteins that were damaged due to the surgical procedure. Proteasomes are more specific markers because there is a correlation between proteasome activity and the type of abdominal surgery in contrast to C-reactive protein concentrations which are not different in response to surgery performed in regard to ovarian cysts or cholelithiasis.
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Intra-Articular Cytokine Levels in Adolescent Patients after Anterior Cruciate Ligament Tear. Mediators Inflamm 2018; 2018:4210593. [PMID: 30245587 PMCID: PMC6136581 DOI: 10.1155/2018/4210593] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 06/22/2018] [Accepted: 07/18/2018] [Indexed: 02/01/2023] Open
Abstract
The treatment of anterior cruciate ligament (ACL) injuries in children and adolescents is challenging. Preclinical and clinical studies investigated ACL repairing techniques in skeletally immature subjects. However, intra-articular bioenvironment following ACL tear has not yet been defined in skeletally immature patients. The aim of this study was to measure cytokine concentrations in the synovial fluid in adolescent population. Synovial levels of IL-1β, IL-1ra, IL-6, IL-8, IL-10, and TNF-α were measured in 17 adolescent patients (15 boys) with ACL tears who underwent ACL reconstruction including acute (5), subacute (7), and chronic (5) phases. Femoral growth plates were classified as “open” in three patients, “closing” in eight, and “closed” in six. Eleven patients presented an ACL tear associated with a meniscal tear. The mean Tegner and Lysholm scores (mean ± SD) of all patients were 8 ± 1 and 50.76 ± 26, respectively. IL-8, TNF-α, and IL-1β levels were significantly greater in patients with “open” physes. IL-1ra and IL-1β levels were significantly higher in patients with ACL tear associated with a meniscal tear. Poor Lysholm scores were associated with elevated IL-6 and IL-10 levels. IL-10 levels positively correlated with IL-6 and IL-8 levels, whereas TNF-α concentration negatively correlated with IL-6 levels. Skeletally immature patients with meniscal tears and open growth plates have a characteristic cytokine profile with particularly elevated levels of proinflammatory cytokines including IL-8, TNF-α, and IL-1β. This picture suggests that the ACL tear could promote an intra-articular catabolic response in adolescent patients greater than that generally reported for adult subjects. The study lacks the comparison with synovial samples from healthy skeletally immature knees due to ethical reasons. Overall, these data contribute to a better knowledge of adolescent intra-articular bioenvironment following ACL injuries.
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Rehabilitation of hamstring strains: does a single injection of platelet-rich plasma improve outcomes? (Clinical study). SPORT SCIENCES FOR HEALTH 2018. [DOI: 10.1007/s11332-018-0474-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Hu Y, Ran J, Zheng Z, Jin Z, Chen X, Yin Z, Tang C, Chen Y, Huang J, Le H, Yan R, Zhu T, Wang J, Lin J, Xu K, Zhou Y, Zhang W, Cai Y, Dominique P, Heng BC, Chen W, Shen W, Ouyang HW. Exogenous stromal derived factor-1 releasing silk scaffold combined with intra-articular injection of progenitor cells promotes bone-ligament-bone regeneration. Acta Biomater 2018. [PMID: 29524675 DOI: 10.1016/j.actbio.2018.02.019] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Anterior cruciate ligament (ACL) is one of the most difficult tissues to heal once injured. Ligament regeneration and tendon-bone junction healing are two major goals of ACL reconstruction. This study aimed to investigate the synergistic therapeutic effects of Stromal cell-derived factor 1 (SDF-1)-releasing collagen-silk (CSF) scaffold combined with intra-articular injection of ligament-derived stem/progenitor cells (LSPCs) for ACL regeneration and the amelioration in the long-term complication of osteoarthritis (OA). The stem cell recruitment ability of CSF scaffold and the multipotency, particularly the tendon forming ability of LSPCs from rabbits were characterized in vitro, while the synergistic effect of the CSF scaffold and LSPCs for ACL regeneration and OA amelioration were investigated in vivo at 1, 3, and 6 months with a rabbit ACL reconstruction model. The CSF scaffold was used as a substitute for the ACL, and LSPCs were injected into the joint cavity after 7 days of the ACL reconstruction. CSF scaffold displayed a controlled release pattern for the encapsulated protein for up to 7 days with an increased stiffness in the mechanical property. LSPCs, which exhibited highly I Collagen and CXCR4 expression, were attracted by SDF-1 and successfully relocated into the CSF scaffold at 1 month in vivo. At 3 and 6 months post-treatment, the CSF scaffold combined with LSPCs (CSFL group) enhanced the regeneration of ACL tissue, and promoted bone tunnel healing. Furthermore, the OA progression was impeded efficiently. Our findings here provided a new strategy that using stem cell recruiting CSF scaffold with tissue-specific stem cells, could be a promising solution for ACL regeneration. STATEMENT OF SIGNIFICANCE In this study, we developed a silk scaffold with increased stiffness and SDF-1 controlled release capacity for ligament repair. This advanced scaffold transplantation combined with intra-articular injection of LSPCs (which was isolated from rabbit ligament for the first time in this study) promoted the regeneration of both the tendinous and bone tunnel portion of ACL. This therapeutic strategy also ameliorated cartilage degeneration and reduced the severity of arthrofibrosis. Hence, combining LSPCs injection with SDF-1-releasing silk scaffold is demonstrated as a therapeutic strategy for ACL regeneration and OA treatment in the clinic.
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Amano K, Huebner JL, Stabler TV, Tanaka M, McCulloch CE, Lobach I, Lane NE, Kraus VB, Benjamin C, Li X. Synovial Fluid Profile at the Time of Anterior Cruciate Ligament Reconstruction and Its Association With Cartilage Matrix Composition 3 Years After Surgery. Am J Sports Med 2018; 46:890-899. [PMID: 29364702 PMCID: PMC7263374 DOI: 10.1177/0363546517749834] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Anterior cruciate ligament tears can lead to posttraumatic osteoarthritis. In addition to biomechanical factors, changes in biochemical profiles within the knee joint after injury and anterior cruciate ligament reconstruction (ACLR) may play a role in accelerating joint degeneration. Hypothesis/Purpose: It was hypothesized that cartilage matrix composition after ACLR is associated with the degree of inflammatory response after initial injury. This study evaluated the association between the inflammatory response after injury-as indicated by cytokine, metalloproteinase, and cartilage degradation marker concentrations in synovial fluid-and articular cartilage degeneration, measured by T1ρ and T2 quantitative magnetic resonance imaging up to 3 years after ACLR. STUDY DESIGN Cohort study; Level of evidence, 2. METHODS Twenty-six subjects from a longitudinal cohort study who underwent ACLR at a mean 8.5 weeks after injury (range, 4-19 weeks) had synovial fluid aspirated at the time of surgery. Immunoassays quantified biomarkers in synovial fluid. T1ρ and T2 values of articular cartilage were calculated with magnetic resonance scans acquired prior to surgery and at 6 months and 1, 2, and 3 years after surgery. Pearson correlation coefficients were calculated among the various biomarkers. K-means clustering was used to group subjects with similar biomarker profiles. Generalized estimating equations were used to find the overall differences in T1ρ and T2 values throughout these first 3 years after surgery between the clusters while controlling for other factors. RESULTS Significant and strong correlations were observed between several cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α) and 2 matrix metalloproteinases (MMP-1 and MMP-3) ( P < .05). Moderate correlations were found among combinations of C-terminal crosslinked telopeptide type II collagen, N-terminal telopeptide, cartilage oligomeric matrix protein, and sulfated glycosaminoglycan ( P < .05). Two clusters were generated, 1 of which was characterized by lower concentrations of cytokines (IL-6, IL-8, IL-10, tumor necrosis factor α) and MMP-1 and MMP-3 and higher sulfated glycosaminoglycan. This cluster was associated with significantly higher T1ρ and T2 values in the medial tibial and patellar cartilage over the first 3 years after ACLR. CONCLUSION At the time of ACLR surgery, profiles of synovial fluid inflammatory cytokines, degradative enzymes, and cartilage breakdown products show promise as predictors of abnormal cartilage tissue integrity (increased T1ρ and T2 values) throughout the first 3 years after surgery. CLINICAL RELEVANCE The results suggest an intricate relationship between inflammation and cartilage turnover, which can in turn be influenced by timing after injury and patient factors.
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Affiliation(s)
- Keiko Amano
- Department of Orthopaedic Surgery, University of California, San Francisco, California, USA
| | - Janet L. Huebner
- Duke Molecular Physiology Institute, School of Medicine, Duke University, Durham, North Carolina, USA
| | - Thomas V. Stabler
- Duke Molecular Physiology Institute, School of Medicine, Duke University, Durham, North Carolina, USA
| | - Matthew Tanaka
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
| | - Charles E. McCulloch
- Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
| | - Iryna Lobach
- Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
| | - Nancy E. Lane
- Division of Rheumatology, UC Davis Health System, University of California, Davis, California, USA
| | - Virginia B. Kraus
- Duke Molecular Physiology Institute and Division of Rheumatology, School of Medicine, Duke University, Durham, North Carolina, USA
| | - C. Benjamin
- Department of Orthopaedic Surgery, University of California, San Francisco, California, USA.,Address correspondence to C. Benjamin Ma, MD, Department of Orthopaedic Surgery, University of California, San Francisco, 1500 Owens St, Rm 200, San Francisco, CA 94158, USA ()
| | - Xiaojuan Li
- Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA
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Healing potential and surgical treatment of anterior cruciate ligament rupture in pediatric population. SPORT SCIENCES FOR HEALTH 2017. [DOI: 10.1007/s11332-017-0375-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Adams SB, Leimer EM, Setton LA, Bell RD, Easley ME, Huebner JL, Stabler TV, Kraus VB, Olson SA, Nettles DL. Inflammatory Microenvironment Persists After Bone Healing in Intra-articular Ankle Fractures. Foot Ankle Int 2017; 38:479-484. [PMID: 28142266 DOI: 10.1177/1071100717690427] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end-stage PTOA remains undefined. This study characterized synovial fluid (SF) composition of ankles after bone healing of an intra-articular fracture to identify factors that may contribute to the development of PTOA. METHODS Of an original 21 patients whose SF was characterized acutely following intra-articular ankle fractures, 7 returned for planned hardware (syndesmotic screw) removal after bone healing (approximately 6 months) and consented to a second bilateral SF collection. SF concentrations of 15 cytokines and matrix metalloproteinases (MMPs) and 2 markers each of cartilage catabolism (CTXII and glycosaminoglycan) and hemarthrosis (biliverdin and bilirubin) were compared for previously fractured and contralateral, uninjured ankles from the same patient. Analysis was also performed to determine the effect of the number of fracture lines and involvement of soft tissue on SF composition. RESULTS Interleukin (IL)-6, IL-8, MMP-1, MMP-2, and MMP-3 were significantly elevated in the SF from healed ankles compared to matched contralateral uninjured ankles at approximately 6 months after fracture. There were no differences in markers of cartilage catabolism or hemarthrosis. Only IL-1α was affected by the number of fracture lines while differences were not detected for other analytes or with respect to the involvment of soft tissue. CONCLUSIONS Sustained intra-articular inflammation, even after complete bone healing, was suggested by elevations of pro-inflammatory cytokines (IL-6 and IL-8). In addition, elevated concentrations of MMPs were also noted and were consistent with a persistent inflammatory environment. This study suggests new evidence of persistent intra-articular inflammation after intra-articular ankle fracture healing and suggests potential mediators for PTOA development. CLINICAL RELEVANCE This work may be relevant to the clinical diagnosis and treatment of post-traumatic osteoarthritis.
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Affiliation(s)
- Samuel B Adams
- 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA
| | - Elizabeth M Leimer
- 2 Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, USA.,3 Albany Medical College, Albany, NY, USA.,4 Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Lori A Setton
- 2 Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, USA
| | - Richard D Bell
- 5 Department of Pathology, Rochester, University of Rochester Medical Center, NY, USA
| | - Mark E Easley
- 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA
| | | | | | - Virginia B Kraus
- 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.,6 Division of Rheumatology and Immunology, Department of Pathology, Duke University Department of Medicine, Durham, NC, USA.,7 Duke Molecular Physiology Institute, Durham, NC, USA
| | - Steven A Olson
- 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA
| | - Dana L Nettles
- 1 Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA
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Bigoni M, Gaddi D, Gorla M, Munegato D, Pungitore M, Piatti M, Turati M. Arthroscopic anterior cruciate ligament repair for proximal anterior cruciate ligament tears in skeletally immature patients: Surgical technique and preliminary results. Knee 2017; 24:40-48. [PMID: 27815015 DOI: 10.1016/j.knee.2016.09.017] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Revised: 09/14/2016] [Accepted: 09/16/2016] [Indexed: 02/02/2023]
Abstract
BACKGROUND Anterior cruciate ligament (ACL) tears in children are increasingly common and present difficult treatment decisions due to the risk of growth disturbance. Although open primary ACL repair was abandoned in the historical literature, recent studies have suggested that there is a role for arthroscopic primary repair in patients with proximal tears. METHODS This is a retrospective review of five consecutive patients aged 9.2years (range 8 to 10) who underwent suture anchor ACL reinsertion. Patients were included if they were Tanner stages 1-2 and proximal ACL tears with adequate tissue quality confirmed arthroscopically. The time frame was 81days. Arthroscopic ACL reinsertion was performed with bioabsorbable suture anchor. Clinical evaluation, KT-1000™, and MRI were re-evaluated. Clinical outcomes were measured using International Knee Documentation Committee (IKDC), Lysholm and Tegner activity score. RESULTS At a mean follow-up of 43.4months (range 25 to 56), no re-injury and leg length discrepancies were observed. Four patients had negative Lachman tests. The remainder had a grade 1 Lachman test. The mean side-to-side difference was 3 (2-4mm). In MRI obtained at the last follow-up, no articular lesions or growth arrest were observed and the reinserted ACL was recognized in every exam. All patients returned to previous level of activity and presented normal and nearly normal IKDC score. The mean Lysholm score was 93.6. CONCLUSION Arthroscopic ACL repair can achieve good short-term results with joint stability and recovery of sport activity in skeletally immature patients, with proximal ACL avulsion tear.
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Affiliation(s)
- Marco Bigoni
- Orthopedic Department, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Diego Gaddi
- Orthopedic Department, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Massimo Gorla
- Orthopedic Department, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Daniele Munegato
- Orthopedic Department, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Marco Pungitore
- Orthopedic Department, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Massimiliano Piatti
- Orthopedic Department, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Marco Turati
- Orthopedic Department, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy.
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Murata K, Kanemura N, Kokubun T, Morishita Y, Fujino T, Takayanagi K. Acute chondrocyte response to controlling joint instability in an osteoarthritis rat model. SPORT SCIENCES FOR HEALTH 2016. [DOI: 10.1007/s11332-016-0320-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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