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Lv X, Wang X, Yue J, Wang X, Chen H, Gao Q. Effect of traction therapy on muscle satellite cell proliferation and differentiation in a rat model of knee stiffness. Stem Cell Res Ther 2024; 15:490. [PMID: 39707518 DOI: 10.1186/s13287-024-04108-1] [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] [Received: 09/20/2024] [Accepted: 12/06/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND In the rat knee stiffness model, the duration of traction treatment is mostly 20-40 min; however, relatively few studies have been conducted on longer traction treatment of extended knee stiffness in rats. Therefore, the aim of this study was to explore the efficacy of prolonged traction and its mechanism of action in extended knee stiffness in rats. METHODS The model of extended knee joint stiffness was established in rats and treated with powered flexion position traction. On the 10th and 20th days respectively, passive range of motion (PROM) assessments and musculoskeletal ultrasound were conducted. Rectus femoris muscle tissues were taken for Western blotting (WB) to detect the expression of muscle satellite cells proliferation and differentiation signaling factors. Histopathological staining was used to evaluate the degree of muscle atrophy and muscle fibrosis in the rectus femoris muscle, and immunofluorescence double staining was used to detect proliferation of muscle satellite cells number. The results from these analyses were used to assess the therapeutic outcomes of the traction treatment. RESULTS The findings indicated that chronic persistent traction significantly improved joint mobility, notably enhanced the proliferation of muscle satellite cells, and inhibited their differentiation. Furthermore, the treatment facilitated the repair and regeneration of damaged tissues, reduced muscular atrophy and fibrosis in the rectus femoris muscle, and alleviated knee stiffness. CONCLUSION Chronic persistent traction can effectively relieve knee joint stiffness, and its mechanism is related to the activation and proliferation of the rectus femoris muscle satellite cells, thereby promoting the repair and regeneration of damaged skeletal muscle.
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Affiliation(s)
- Xiaoqian Lv
- The Second Affiliated Hospital of Bengbu Medical University, Bengbu, 233040, China
| | - Xiaoyu Wang
- The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China
| | - Jianxing Yue
- The Second Affiliated Hospital of Bengbu Medical University, Bengbu, 233040, China
| | - Xin Wang
- The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China
| | - Haoyue Chen
- The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China
| | - Qiang Gao
- The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China.
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Zhou CX, Wang F, Zhou Y, Fang QZ, Zhang QB. Formation process of extension knee joint contracture following external immobilization in rats. World J Orthop 2023; 14:669-681. [PMID: 37744718 PMCID: PMC10514713 DOI: 10.5312/wjo.v14.i9.669] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/30/2023] [Accepted: 08/21/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Current research lacks a model of knee extension contracture in rats.
AIM To elucidate the formation process of knee extension contracture.
METHODS We developed a rat model using an aluminum external fixator. Sixty male Sprague-Dawley rats with mature bones were divided into the control group (n = 6) and groups that had the left knee immobilized with an aluminum external fixator for 1, 2, and 3 d, and 1, 2, 3, 4, 6, and 8 wk (n = 6 in each group). The passive extension range of motion, histology, and expression of fibrosis-related proteins were compared between the control group and the immobilization groups.
RESULTS Myogenic contracture progressed very quickly during the initial 2 wk of immobilization. After 2 wk, the contracture gradually changed from myogenic to arthrogenic. The arthrogenic contracture progressed slowly during the 1st week, rapidly progressed until the 3rd week, and then showed a steady progression until the 4rd week. Histological analyses confirmed that the anterior joint capsule of the extended fixed knee became increasingly thicker over time. Correspondingly, the level of transforming growth factor beta 1 (TGF-β1) and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2) in the anterior joint capsule also increased with the immobilization time. Over time, the cross-sectional area of muscle fibers gradually decreased, while the amount of intermuscular collagen and TGF-β1, p-Smad2, and p-Smad3 was increased. Unexpectedly, the amount of intermuscular collagen and TGF-β1, p-Smad2, and p-Smad3 was decreased during the late stage of immobilization (6-8 wk). The myogenic contracture was stabilized after 2 wk of immobilization, whereas the arthrogenic contracture was stabilized after 3 wk of immobilization and completely stable in 4 wk.
CONCLUSION This rat model may be a useful tool to study the etiology of joint contracture and establish therapeutic approaches.
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Affiliation(s)
- Chen-Xu Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Feng Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Yun Zhou
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Qiao-Zhou Fang
- The Second Clinical Medicine College, Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Quan-Bing Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
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Kaneguchi A, Ozawa J. Inflammation and Fibrosis Induced by Joint Remobilization, and Relevance to Progression of Arthrogenic Joint Contracture: A Narrative Review. Physiol Res 2022. [DOI: 10.33549/physiolres.934876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Joint immobilization is frequently administered after fractures and ligament injuries and can cause joint contracture as a side effect. The structures responsible for immobilization-induced joint contracture can be roughly divided into muscular and articular. During remobilization, although myogenic contracture recovers spontaneously, arthrogenic contracture is irreversible or deteriorates further. Immediately after remobilization, an inflammatory response is observed, characterized by joint swelling, deposit formation in the joint space, edema, inflammatory cell infiltration, and the upregulation of genes encoding proinflammatory cytokines in the joint capsule. Subsequently, fibrosis in the joint capsule develops, in parallel with progressing arthrogenic contracture. The triggers of remobilization-induced joint inflammation are not fully understood, but two potential mechanisms are proposed: 1) micro-damage induced by mechanical stress in the joint capsule, and 2) nitric oxide (NO) production via NO synthase 2. Some interventions can modulate remobilization-induced inflammatory and subsequent fibrotic reactions. Anti-inflammatory treatments, such as steroidal anti-inflammatory drugs and low-level laser therapy, can attenuate joint capsule fibrosis and the progression of arthrogenic contracture in remobilized joints. Antiproliferative treatment using the cell-proliferation inhibitor mitomycin C can also attenuate joint capsule fibrosis by inhibiting fibroblast proliferation without suppressing inflammation. Conversely, aggressive exercise during the early remobilization phases is counterproductive, because it facilitates inflammatory and then fibrotic reactions in the joint. However, the adverse effects of aggressive exercise on remobilization-induced inflammation and fibrosis are offset by anti-inflammatory treatment. To prevent the progression of arthrogenic contracture during remobilization, therefore, care should be taken to control inflammatory and fibrotic reactions in the joints.
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Affiliation(s)
- A Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan
| | - J Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan.
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Zhang S, Song J, Wu Q, Fang J, Ning B. Collagen I in the Hip Capsule Plays a Role in Postoperative Clinical Function in Patients With Developmental Dysplasia of the Hip. Front Pediatr 2022; 10:918660. [PMID: 35633968 PMCID: PMC9130651 DOI: 10.3389/fped.2022.918660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 04/22/2022] [Indexed: 11/13/2022] Open
Abstract
The aims of the present study is to evaluate the roles of collagen I and III in the hip capsule in the postoperative clinical function of patients with developmental dysplasia of the hip (DDH). Hip capsules from 155 hips of 120 patients were collected during surgery. The patients were divided into three groups according to age: I: 2-3.5 years; II: 3.5-5 years; and III: 5-6 years. Patient clinical function and radiographic outcomes were evaluated with the McKay scores and Severin classification. The expression of collagen I and III was detected through immunohistochemistry and quantitative reverse transcription polymerase chain reaction (RT-PCR) and analyzed according to age, sex, degree of dislocation and McKay classification. All patients received open reduction and pelvic osteotomy and/or femoral shortening osteotomy and achieved good results on the basis of postoperative X-ray imaging. The average follow-up time was 3.4 years (range 2-4.3 years). There were no changes in the expression of collagen III in the different groups. The expression of collagen I according to age and sex was not significantly different. Lower expression of collagen I was observed in DDH patients with a higher degree of dislocation according to the Tonnis grade. The highest expression of collagen I was detected in the group with poor clinical function according to the McKay classification. Collagen I is correlated with the degree of dislocation and is a risk factor for poor clinical function in DDH patients. Collagen I is correlated with the degree of hip dislocation and poor clinical function in DDH patients.
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Affiliation(s)
- Sicheng Zhang
- Department of Pediatric Orthopaedic, Anhui Provincial Children's Hospital, Hefei, China
| | - Jun Song
- Children's Hospital, Fudan University, Shanghai, China
| | - Qingjie Wu
- Anhui Provincial Children's Hospital, Hefei, China
| | - Jihong Fang
- Anhui Provincial Children's Hospital, Hefei, China
| | - Bo Ning
- Children's Hospital, Fudan University, Shanghai, China
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Sogi Y, Yabe Y, Hagiwara Y, Tsuchiya M, Onoda Y, Sekiguchi T, Itaya N, Yoshida S, Yano T, Suzuki K, Onoki T, Itoi E. Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model. BMC Musculoskelet Disord 2020; 21:761. [PMID: 33213419 PMCID: PMC7678279 DOI: 10.1186/s12891-020-03795-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 11/12/2020] [Indexed: 01/05/2023] Open
Abstract
Background Joint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorders such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis and oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although joint hemorrhage has negative effects on the articular cartilage, there is no consensus on whether a reduction in joint hemorrhage would effectively prevent articular cartilage degeneration. The purpose of this study was to investigate the effect of joint hemorrhage combined with joint immobilization on articular cartilage degeneration in a rat immobilized knee model. Methods The knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were randomly divided into the following groups: immobilized blood injection (Im-B) and immobilized-normal saline injection (Im-NS) groups. The cartilage was evaluated in two areas (contact and non-contact areas). The cartilage was used to assess chondrocyte count, Modified Mankin score, and cartilage thickness. The total RNA was extracted from the cartilage in both areas, and the expression of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was measured by quantitative real-time polymerase chain reaction. Results The number of chondrocytes in the Im-B group significantly decreased in both areas, compared with that in the Im-NS group. Modified Mankin score from 4 to 8 weeks of the Im-B group was significantly higher than that of the Im-NS group only in the contact area. The expression of MMP-8 and MMP-13 from 2 to 4 weeks and TNF-α from 2 to 8 weeks significantly increased in the Im-B group compared with those in the Im-NS group, but there was no significant difference in IL-1β expression. Conclusions The results showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Drainage of a joint hemorrhage or avoidance of loading may help prevent cartilage degeneration during joint immobilization with a hemorrhage. Supplementary Information The online version contains supplementary material available at 10.1186/s12891-020-03795-0.
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Affiliation(s)
- Yasuhito Sogi
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Yutaka Yabe
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Yoshihiro Hagiwara
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
| | - Masahiro Tsuchiya
- Department of Nursing, Faculty of Health Science, Tohoku Fukushi University, 1-8-1 Kunimi, Aoba-ku, Sendai, 981-8522, Japan
| | - Yoshito Onoda
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Takuya Sekiguchi
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Nobuyuki Itaya
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Shinichiro Yoshida
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Toshihisa Yano
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Kazuaki Suzuki
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Takahiro Onoki
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Eiji Itoi
- Department of Orthopaedic Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
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Kaneguchi A, Ozawa J, Yamaoka K. Intra-articular injection of mitomycin C prevents progression of immobilization-induced arthrogenic contracture in the remobilized rat knee. Physiol Res 2020; 69:145-156. [PMID: 31852201 DOI: 10.33549/physiolres.934149] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
This study tested whether cell cycle inhibitor mitomycin C (MMC) prevents arthrogenic contracture progression during remobilization by inhibiting fibroblast proliferation and fibrosis in the joint capsule. Rat knees were immobilized in a flexed position to generate flexion contracture. After three weeks, the fixation device was removed and rat knees were allowed to freely move for one week. Immediately after and three days after fixator removal, rats received intra-articular injections of MMC or saline. The passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors to distinguish myogenic and arthrogenic contractures. In addition, both cellularity and fibrosis in the posterior joint capsule were assessed histologically. Joint immobilization significantly decreased ROMs both before and after myotomy compared with untreated controls. In saline-injected knees, remobilization increased ROM before myotomy, but further decreased that after myotomy compared with that of knees immediately after three weeks of immobilization. Histological analysis revealed that hypercellularity, mainly due to fibroblast proliferation, and fibrosis characterized by increases in collagen density and joint capsule thickness occurred after remobilization in saline-injected knees. Conversely, MMC injections were able to prevent the remobilization-enhanced reduction of ROM after myotomy by inhibiting both hypercellularity and joint capsule fibrosis. Our results suggest that joint capsule fibrosis accompanied by fibroblast proliferation is a potential cause of arthrogenic contracture progression during remobilization, and that inhibiting fibroblast proliferation may constitute an effective remedy.
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Affiliation(s)
- A Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Hiroshima, Japan.
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Baranowski A, Schlemmer L, Förster K, Slotina E, Mickan T, Truffel S, Klein A, Mattyasovszky SG, Hofmann A, Ritz U, Rommens PM. Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model. Drug Des Devel Ther 2019; 13:2603-2618. [PMID: 31440039 PMCID: PMC6679684 DOI: 10.2147/dddt.s204135] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 06/27/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems. OBJECTIVE The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed. STUDY DESIGN AND METHODS In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were immobilized with a Kirschner wire. Rats received either losartan, atorvastatin or a placebo orally daily. After 14 days, joint angle measurements and histological assessments were performed. RESULTS Losartan increased the length of the inferior joint capsule. Joint angle and other capsule length measurements did not reveal significant differences between both drugs and the placebo. At cellular level both losartan and atorvastatin reduced the total number of myofibroblasts (losartan: 191±77, atorvastatin: 98±58, placebo: 319±113 per counting field, p<0.01) and the percentage area of myofibroblasts (losartan: 2.8±1.8% [p<0.05], atorvastatin: 2.5±1.7% [p<0.01], vs control [6.4±4%], respectively). BSP was detectable in equivalent amounts in the joint capsules of all groups with only a trend toward a reduction of the BSP-stained area by atorvastatin. CONCLUSION Both atorvastatin and losartan reduced the number of myofibroblasts in the posterior knee joint capsule of rat knees 2 weeks after trauma and losartan increased the length of the inferior joint capsule. However, these changes at the cellular level did not translate an increase in range of motion of the rats´ knee joints during early contracture development.
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Affiliation(s)
- Andreas Baranowski
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Ludwig Schlemmer
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Katharina Förster
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Ekaterina Slotina
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Tim Mickan
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Sebastian Truffel
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Anja Klein
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Stefan G Mattyasovszky
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Alexander Hofmann
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
- Department of Traumatology and Orthopaedics 1, Westpfalz-Medical Centre Kaiserslautern, Kaiserslautern, Germany
| | - Ulrike Ritz
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Pol M Rommens
- Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
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Ando A, Hagiwara Y, Onoda Y, Hatori K, Suda H, Chimoto E, Itoi E. Distribution of Type A and B Synoviocytes in the Adhesive and Shortened Synovial Membrane during Immobilization of the Knee Joint in Rats. TOHOKU J EXP MED 2010; 221:161-8. [DOI: 10.1620/tjem.221.161] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Akira Ando
- Department of Orthopaedic Surgery, Tohoku University School of Medicine
| | - Yoshihiro Hagiwara
- Department of Orthopaedic Surgery, Tohoku University School of Medicine
- Department of Orthopaedic Surgery, Takeda General Hospital
| | - Yoshito Onoda
- Department of Orthopaedic Surgery, Tohoku University School of Medicine
| | - Kouki Hatori
- Division of Advanced Prosthetic Dentistry, Tohoku University School of Dentistry
| | - Hideaki Suda
- Department of Orthopaedic Surgery, Tohoku University School of Medicine
| | - Eiichi Chimoto
- Department of Orthopaedic Surgery, Tohoku University School of Medicine
| | - Eiji Itoi
- Department of Orthopaedic Surgery, Tohoku University School of Medicine
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