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Barone S, Cevidanes L, Bianchi J, Goncalves JR, Giudice A. Deep Learning-Based Three-Dimensional Analysis Reveals Distinct Patterns of Condylar Remodelling After Orthognathic Surgery in Skeletal Class III Patients. Orthod Craniofac Res 2025; 28:441-448. [PMID: 39754473 PMCID: PMC12056474 DOI: 10.1111/ocr.12895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 12/19/2024] [Accepted: 12/24/2024] [Indexed: 01/06/2025]
Abstract
OBJECTIVE This retrospective study aimed to evaluate morphometric changes in mandibular condyles of patients with skeletal Class III malocclusion following two-jaw orthognathic surgery planned using virtual surgical planning (VSP) and analysed with automated three-dimensional (3D) image analysis based on deep-learning techniques. MATERIALS AND METHODS Pre-operative (T1) and 12-18 months post-operative (T2) Cone-Beam Computed Tomography (CBCT) scans of 17 patients (mean age: 24.8 ± 3.5 years) were analysed using 3DSlicer software. Deep-learning algorithms automated CBCT orientation, registration, bone segmentation, and landmark identification. By utilising voxel-based superimposition of pre- and post-operative CBCT scans and shape correspondence, the overall changes in condylar morphology were assessed, with a focus on bone resorption and apposition at specific regions (superior, lateral and medial poles). The correlation between these modifications and the extent of actual condylar movements post-surgery was investigated. Statistical analysis was conducted with a significance level of α = 0.05. RESULTS Overall condylar remodelling was minimal, with mean changes of < 1 mm. Small but statistically significant bone resorption occurred at the condylar superior articular surface, while bone apposition was primarily observed at the lateral pole. The bone apposition at the lateral pole and resorption at the superior articular surface were significantly correlated with medial condylar displacement (p < 0.05). CONCLUSION The automated 3D analysis revealed distinct patterns of condylar remodelling following orthognathic surgery in skeletal Class III patients, with minimal overall changes but significant regional variations. The correlation between condylar displacements and remodelling patterns highlights the need for precise pre-operative planning to optimise condylar positioning, potentially minimising harmful remodelling and enhancing stability.
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Affiliation(s)
- Selene Barone
- Department of Health Sciences, School of DentistryMagna Graecia University of CatanzaroCatanzaroItaly
| | - Lucia Cevidanes
- Department of Orthodontics and Pediatric Dentistry, School of DentistryUniversity of MichiganAnn ArborMichiganUSA
| | - Jonas Bianchi
- Dugoni School of DentistryUniversity of the PacificSan FranciscoCaliforniaUSA
| | | | - Amerigo Giudice
- Department of Health Sciences, School of DentistryMagna Graecia University of CatanzaroCatanzaroItaly
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Zhang Y, Zheng X, Zhang Q, He Z, Huang W, Yan X, Lv T, Yuan X. Clinical finite element analysis of mandibular displacement model treated with Twin-block appliance. Am J Orthod Dentofacial Orthop 2023; 164:395-405. [PMID: 37029052 DOI: 10.1016/j.ajodo.2023.02.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 02/01/2023] [Accepted: 02/01/2023] [Indexed: 04/09/2023]
Abstract
INTRODUCTION The mechanical distribution of the mandible is an important factor that affects functional orthosis during Twin-block (TB) appliance correction. Changes in the mandible before and after TB appliance correction are also key factors in maintaining the therapeutic effect. Finite element analysis, a powerful numerical, analytical tool, is widely used to predict the stress and strain distribution of the craniofacial bone that orthodontics generates. METHODS The sample was a 14-year-old male patient with Class II malocclusion during growth. A cone-beam computed tomography scan was undertaken at pretreatment and posttreatment. In the Finite element analysis of the pretreatment model, the remote displacement model of the mandible was established with the sella point as the center. A mandibular model under TB appliance loading was established. Its mandibular displacement and von Mises stress were compared before and after loading. Three-dimensional registration was conducted on the pretreatment and posttreatment models to measure the sagittal displacement of the centrosome. RESULTS The force on the mandible occurred mainly in the condyle neck and medial mandible after the TB appliance moved the mandible. After displacement, the posterior upper margin of the condyle was farther away from the articular fossa. Three-dimensional registration results showed that new bone had formed behind and above the condyle after TB appliance treatment. CONCLUSION The TB appliance provides additional advantages in treating skeletal Class II malocclusions by helping to reduce the burden on the temporomandibular joint and promoting the adaptive reconstruction of the mandible.
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Affiliation(s)
- Yingyue Zhang
- Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China; School of Stomatology, Qingdao University, Qingdao, China
| | - Xinyu Zheng
- Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China; School of Stomatology, Qingdao University, Qingdao, China
| | - Qiang Zhang
- Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China; School of Stomatology, Qingdao University, Qingdao, China
| | - Zijing He
- Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China; School of Stomatology, Qingdao University, Qingdao, China
| | - Wenli Huang
- Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China; School of Stomatology, Qingdao University, Qingdao, China
| | - Xiao Yan
- Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China; School of Stomatology, Qingdao University, Qingdao, China
| | - Tao Lv
- Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Qingdao, China.
| | - Xiao Yuan
- Department of Orthodontics, The Affiliated Hospital of Qingdao University, Qingdao, China; School of Stomatology, Qingdao University, Qingdao, China.
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Nicot R, Chung K, Vieira AR, Raoul G, Ferri J, Sciote JJ. Condyle modeling stability, craniofacial asymmetry and ACTN3 genotypes: Contribution to TMD prevalence in a cohort of dentofacial deformities. PLoS One 2020; 15:e0236425. [PMID: 32726330 PMCID: PMC7390436 DOI: 10.1371/journal.pone.0236425] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 07/06/2020] [Indexed: 01/01/2023] Open
Abstract
Craniofacial asymmetry, mandibular condylar modeling and temporomandibular joint disorders are common comorbidities of skeletally disproportionate malocclusions, but etiology of occurrence together is poorly understood. We compared asymmetry, condyle modeling stability and temporomandibular health in a cohort of 128 patients having orthodontics and orthognathic surgery to correct dentofacial deformity malocclusions. We also compared ACTN3 and ENPP1 genotypes for association to clinical conditions. Pre-surgical posterior-anterior cephalometric and panometric radiographic analyses; jaw pain and function questionnaire and clinical examination of TMD; and SNP-genotype analysis from saliva samples were compared to assess interrelationships. Almost half had asymmetries in need of surgical correction, which could be subdivided into four distinct morphological patterns. Asymmetric condyle modeling between sides was significantly greater in craniofacial asymmetry, but most commonly had an unanticipated pattern. Often, longer or larger condyles occurred on the shorter mandibular ramus side. Subjects with longer ramus but dimensionally smaller condyles were more likely to have self-reported TMD symptoms (p = 0.023) and significantly greater clinical diagnosis of TMD (p = 0 .000001), with masticatory myalgia most prominent. Genotyping found two significant genotype associations for ACTN3 rs1671064 (Q523R missense) p = 0.02; rs678397 (intronic SNP) p = 0.04 and one significant allele association rs1815739 (R577X nonsense) p = 0.00. Skeletal asymmetry, unusual condyle modeling and TMD are common and interrelated components of many dentofacial deformities. Imbalanced musculoskeletal functional adaptations and genetic or epigenetic influences contribute to the etiology, and require further investigation.
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Affiliation(s)
- Romain Nicot
- Department of Oral and Maxillofacial Surgery, Univ. Lille, Inserm, CHU Lille, U1008—Controlled Drug Delivery Systems and Biomaterials, Lille, France
- * E-mail:
| | - Kay Chung
- Department of Orthodontics, Temple University, Philadelphia, PA, United States of America
| | - Alexandre R. Vieira
- Department of Oral Biology, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, United States of America
| | - Gwénaël Raoul
- Department of Oral and Maxillofacial Surgery, Univ. Lille, Inserm, CHU Lille, U1008—Controlled Drug Delivery Systems and Biomaterials, Lille, France
| | - Joël Ferri
- Department of Oral and Maxillofacial Surgery, Univ. Lille, Inserm, CHU Lille, U1008—Controlled Drug Delivery Systems and Biomaterials, Lille, France
| | - James J. Sciote
- Department of Orthodontics, Temple University, Philadelphia, PA, United States of America
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Chen J, He Y, Keilig L, Reimann S, Hasan I, Weinhold J, Radlanski R, Bourauel C. Numerical investigations of bone remodelling around the mouse mandibular molar primordia. Ann Anat 2019; 222:146-152. [DOI: 10.1016/j.aanat.2018.12.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 11/07/2018] [Accepted: 12/18/2018] [Indexed: 11/25/2022]
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Karamesinis K, Basdra EK. The biological basis of treating jaw discrepancies: An interplay of mechanical forces and skeletal configuration. Biochim Biophys Acta Mol Basis Dis 2018; 1864:1675-1683. [PMID: 29454076 DOI: 10.1016/j.bbadis.2018.02.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 02/06/2018] [Accepted: 02/12/2018] [Indexed: 10/18/2022]
Abstract
Jaw discrepancies and malrelations affect a large proportion of the general population and their treatment is of utmost significance for individuals' health and quality of life. The aim of their therapy is the modification of aberrant jaw development mainly by targeting the growth potential of the mandibular condyle through its cartilage, and the architectural shape of alveolar bone through a suture type of structure, the periodontal ligament. This targeted treatment is achieved via external mechanical force application by using a wide variety of intraoral and extraoral appliances. Condylar cartilage and sutures exhibit a remarkable plasticity due to the mechano-responsiveness of the chondrocytes and the multipotent mesenchymal cells of the sutures. The tissues respond biologically and adapt to mechanical force application by a variety of signaling pathways and a final interplay between the proliferative activity and the differentiation status of the cells involved. These targeted therapeutic functional alterations within temporo-mandibular joint ultimately result in the enhancement or restriction of mandibular growth, while within the periodontal ligament lead to bone remodeling and change of its architectural structure. Depending on the form of the malrelation presented, the above treatment approaches, in conjunction or separately, lead to the total correction of jaw discrepancies and the achievement of facial harmony and function. Overall, the treatment of craniofacial and jaw anomalies can be seen as an interplay of mechanical forces and adaptations occurring within temporo-mandibular joint and alveolar bone. The aim of the present review is to present up-to-date knowledge on the mechano-biology behind jaw growth modification and alveolar bone remodeling. Furthermore, future molecular targeted therapeutic strategies are discussed aiming at the improvement of mechanically-driven chondrogenesis and osteogenesis.
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Affiliation(s)
- Konstantinos Karamesinis
- Department of Biological Chemistry, Cellular and Molecular Biomechanics Unit, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Efthimia K Basdra
- Department of Biological Chemistry, Cellular and Molecular Biomechanics Unit, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
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Yu J, Liang F, Huang H, Pirttiniemi P, Yu D. Effects of loading on chondrocyte hypoxia, HIF-1α and VEGF in the mandibular condylar cartilage of young rats. Orthod Craniofac Res 2017; 21:41-47. [PMID: 29271061 DOI: 10.1111/ocr.12212] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/22/2017] [Indexed: 12/19/2022]
Abstract
OBJECTIVES To investigate hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) expression under altered loading, and to explore the relationship between loading and hypoxia in the mandibular condylar cartilage of young rats. SETTING AND SAMPLE POPULATION Eighty Sprague-Dawley rats. MATERIAL AND METHODS The reduced loading group was fed soft food, and their incisors were cut to avoid occlusal contact. The increased loading group was fed hard food and had forced jaw-opening. Ten rats from each group (n = 10) were sacrificed at 12, 24, 48, and 96 hours after initiation of the experiment. Pimonidazole hydrochloride (Hypoxyprobe-1, HP-1) was used as a hypoxia marker to confirm the hypoxic state. Hypoxic chondrocytes as indicated by HP-1, HIF-1α and VEGF protein expressions were recognized by immunohistochemical detection. HIF-1α and VEGF mRNA expressions were detected by semi-quantitative RT-PCR. RESULTS Hypoxyprobe-1 was confined in the upper layers of cartilage, and was most strongly expressed in the weight-bearing area of TMJ at 12 and 96 hours. Staining of HIF-1α and VEGF was most strongly expressed in the chondrocytes of the fibrous and proliferative layer at all time points. Furthermore, expressions were also displayed in the hypertrophic and calcified layers at 48 and 96 hours. The expressions of HIF-1α and VEGF mRNA were higher in the increased loading group than in the reduced loading group at 48 and 96 hours (P < . 05). CONCLUSION Mechanical loading seems to directly induce weight-bearing area hypoxia followed by new vessel formation, which indicates that these factors are related and important for the development of cartilage.
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Affiliation(s)
- J Yu
- Department of Oral Development and Orthodontics, Institute of Dentistry, University of Oulu, Oulu, Finland
| | - F Liang
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Guangxi Medical University, Nanning, China
| | - H Huang
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Guangxi Medical University, Nanning, China
| | - P Pirttiniemi
- Department of Oral Development and Orthodontics, Institute of Dentistry, University of Oulu, Oulu, Finland
| | - D Yu
- Department of Stomatology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Jiang L, Xie Y, Wei L, Zhou Q, Shen X, Jiang X, Gao Y. Identification of the vascular endothelial growth factor signalling pathway by quantitative proteomic analysis of rat condylar cartilage. FEBS Open Bio 2016; 7:44-53. [PMID: 28097087 PMCID: PMC5221432 DOI: 10.1002/2211-5463.12155] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Revised: 10/03/2016] [Accepted: 10/24/2016] [Indexed: 02/05/2023] Open
Abstract
Angiogenesis mediated by vascular endothelial growth factor (VEGF) is known to play an important role in regulating cartilage remodelling and endochondral ossification. However, the details of how VEGF signalling mechanisms affect condyle remodelling in response to alterations in functional loading remains unclear. To explore this, eighty 16‐day‐old male SD rats were divided into two equal groups which were fed either a soft/powdery diet or a hard diet for 4 weeks; the stiffness of the diet results in alteration of mastication force and hence temporomandibular joint (TMJ) development. We performed a proteomic analysis of rat condylar cartilage using isobaric tags for relative and absolute quantification (iTRAQ) labelling, followed by 2D nano‐high performance liquid chromatography and MALDI‐TOF/time‐of‐flight technology. After protein identification, we used biological information analysis to identify the differentially expressed proteins associated with the VEGF signalling pathway. Among the identified differentially expressed proteins, we found VEGF signalling mainly via the p44/42 MAPK and p38 mitogen‐activated protein kinase (MAPK) pathways in condylar cartilage, including VEGFD, VGFR2, KPCB, KPCT, KPCZ, ARAF, RASN, PLCG2, PLCG1, JUN and M3K12. Furthermore, four representative protein candidates, VEGF, p38 MAPK and p44/42 MAPK/phospho‐p44/42 MAPK, were confirmed by immunohistochemical staining and western blot. Our data suggest that VEGF might play an important role in TMJ development and remodelling in response to alterations in functional loading through the p44/42 MAPK and p38 MAPK signalling pathway. This study provides new clues to the understanding of the signalling mechanism responsible for VEGF production in response to different masticatory functions at the protein level.
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Affiliation(s)
- Liting Jiang
- Department of Stomatology Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine China; Department of Prosthodontics Shanghai Key Laboratory of Stomatology Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine China
| | - Yinyin Xie
- State Key Laboratory of Medical Genomics Shanghai Institute of Hematology Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine China
| | - Li Wei
- Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine China
| | - Qi Zhou
- Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine China
| | - Xing Shen
- Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine China
| | - Xinquan Jiang
- Department of Prosthodontics Shanghai Key Laboratory of Stomatology Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine China
| | - Yiming Gao
- Department of Stomatology Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine China
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Tyan S, Kim HH, Park KH, Kim SJ, Kim KA, Ahn HW. Sequential changes of postoperative condylar position in patients with facial asymmetry. Angle Orthod 2016; 87:260-268. [PMID: 27529733 DOI: 10.2319/030916-203.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVE To evaluate sequential images of the condylar position in relation to the glenoid fossa after orthognathic surgery in patients with facial asymmetry using cone beam computed tomography. MATERIALS AND METHODS A total of 20 adult patients (11 men and 9 women; mean age, 22.1 ± 4.02 years) with facial asymmetry who underwent sagittal split ramus osteotomy with rigid fixation were involved. Cone beam computed tomography scans were obtained before treatment (T0), 1 month before the surgery (T1), and 1 day (T2), 3 months (T3), 6 months (T4), and 12 months (T5) after the surgery. The condyle position was evaluated. RESULTS At 1 day after surgery (T2), the condylar position on both sides significantly changed posteriorly, inferiorly, and laterally, but no significant difference was observed between the nonaffected and affected sides. The condyle on the nonaffected side had a tendency to recover its preoperative position at 3 months after surgery (T3) and inclined slightly laterally up to 1 year after the surgery (T5). The condyle on the affected side returned more closely to the glenoid fossa than to its pretreatment position at 3 months after surgery (T3). Thereafter, it showed a more backward and downward position (T5). CONCLUSIONS The overall condylar position after an orthognathic surgery in patients with facial asymmetry was relatively stable at 1 year after surgery. However, the condyle on the affected side during the first 3 months after surgery should be carefully monitored for surgical stability.
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Koletsi D, Eliades T, Zinelis S, Bourauel C, Eliades G. Disease and functional loading effect on the structural conformation and mechanical properties of the mandibular condyle in a transgenic rheumatoid arthritis murine model: an experimental study. Eur J Orthod 2016; 38:615-620. [PMID: 26888831 DOI: 10.1093/ejo/cjw010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
AIM The aim of the present study was to investigate the effect of rheumatoid arthritis (RA) and functional loading through diet modification on the structural conformation and the mechanical properties of the mandibular condyle in a transgenic mouse model and compare to healthy littermates. MATERIALS AND METHODS Four-week-old hybrid male mice from mixed background CBAxC57BL/6 were used. Four groups of animals were formed consisting of five animals each, either presenting RA (transgenic line hTNF 197), or wild-type (control), half receiving ordinary (hard) diet and half receiving soft diet within each category. Following sacrifice, resin-embedded and metallographically polished condylar specimens were evaluated employing scanning electron microscopy/ Energy dispersive x-ray spectroscopy and also tested for mechanical properties, through Vickers microhardness (HV100) measurements. RESULTS The multivariable analysis revealed significantly lower HV100 values for the RA groups after adjusting for diet (β = -10; 95% confidence interval: -16, -4; P = 0.001), while functional loading through diet modification did not appear as a significant predictor of the outcome. CONCLUSIONS There was evidence of compromised mechanical properties of the mandibular condylar bone for the diseased animals, whereas no association between functional loading and mechanical properties of the condyle could be established.
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Affiliation(s)
- Despina Koletsi
- Department of Oral Technology, School of Dentistry, University of Bonn, Germany, Departments of.,Orthodontics and.,Dental Biomaterials, School of Dentistry, University of Athens, Greece, and
| | - Theodore Eliades
- Clinic of Orthodontics and Paediatric Dentistry, Center of Dental Medicine, University of Zurich, Switzerland
| | - Spiros Zinelis
- Dental Biomaterials, School of Dentistry, University of Athens, Greece, and
| | - Christoph Bourauel
- Department of Oral Technology, School of Dentistry, University of Bonn, Germany, Departments of
| | - George Eliades
- Dental Biomaterials, School of Dentistry, University of Athens, Greece, and
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Utreja A, Dyment NA, Yadav S, Villa MM, Li Y, Jiang X, Nanda R, Rowe DW. Cell and matrix response of temporomandibular cartilage to mechanical loading. Osteoarthritis Cartilage 2016; 24:335-44. [PMID: 26362410 PMCID: PMC4757844 DOI: 10.1016/j.joca.2015.08.010] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Revised: 07/01/2015] [Accepted: 08/18/2015] [Indexed: 02/02/2023]
Abstract
OBJECTIVES The generation of transgenic mice expressing green fluorescent proteins (GFPs) has greatly aided our understanding of the development of connective tissues such as bone and cartilage. Perturbation of a biological system such as the temporomandibular joint (TMJ) within its adaptive remodeling capacity is particularly useful in analyzing cellular lineage progression. The objectives of this study were to determine: (i) if GFP reporters expressed in the TMJ indicate the different stages of cell maturation in fibrocartilage and (ii) how mechanical loading affects cellular response in different regions of the cartilage. DESIGN/METHODS Four-week-old transgenic mice harboring combinations of fluorescent reporters (Dkk3-eGFP, Col1a1(3.6 kb)-GFPcyan, Col1a1(3.6 kb)-GFPtpz, Col2a1-GFPcyan, and Col10a1-RFPcherry) were used to analyze the expression pattern of transgenes in the mandibular condylar cartilage (MCC). To study the effect of TMJ loading, animals were subjected to forced mouth opening with custom springs exerting 50 g force for 1 h/day for 5 days. Dynamic mineralization and cellular proliferation (EdU-labeling) were assessed in loaded vs control mice. RESULTS Dkk3 expression was seen in the superficial zone of the MCC, followed by Col1 in the cartilage zone, Col2 in the prehypertrophic zone, and Col10 in the hypertrophic zone at and below the tidemark. TMJ loading increased expression of the GFP reporters and EdU-labeling of cells in the cartilage, resulting in a thickness increase of all layers of the cartilage. In addition, mineral apposition increased resulting in Col10 expression by unmineralized cells above the tidemark. CONCLUSION The TMJ responded to static loading by forming thicker cartilage through adaptive remodeling.
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Affiliation(s)
- A Utreja
- Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, IN 46202, USA
| | - N A Dyment
- Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06032, USA
| | - S Yadav
- Department of Orthodontics, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06032, USA
| | - M M Villa
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA
| | - Y Li
- Biology Department, College of Arts and Sciences, University of Hartford, West Hartford, CT 06117, USA
| | - X Jiang
- Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06032, USA
| | - R Nanda
- Department of Orthodontics, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06032, USA
| | - D W Rowe
- Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT 06032, USA.
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Koletsi D, Eliades T, Zinelis S, Makou M, Bourauel C, Eliades G. The effect of rheumatoid arthritis and functional loading on the structure of the mandibular condyle in a transgenic mouse model: An FTIR study. Arch Oral Biol 2015; 61:44-52. [PMID: 26513681 DOI: 10.1016/j.archoralbio.2015.10.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Accepted: 10/06/2015] [Indexed: 01/05/2023]
Abstract
OBJECTIVE The objective of the present study was to investigate the effect of rheumatoid arthritis and functional loading through diet modification on the biochemical properties of the mandibular condyle in a transgenic mouse model and compare with healthy littermates. DESIGN Twenty three, 4-week old hybrid male mice were used. Eleven were of transgenic line hTNF 197 (Tg 197 - with rheumatoid arthritis - RA) and 12 healthy littermates, both from mixed background CBAxC57BL/6. Four groups of mice were formed. Group 1 [n =5, RA-hard] included transgenic mice and received ordinary (hard) diet; group 2 [n=6, RA-soft] included transgenic line and received soft diet; group 3 [n=6, control-hard] were healthy littermates receiving ordinary (hard) diet and group 4 [n=6, control-soft] were healthy littermates with soft diet. Experimental period was 28 days. Following sacrifice, the mandibular condyles were subjected to micro-attenuated reflection Fourier transform infrared spectroscopy (micro-ATR FTIR) to reveal collagen/proteoglycan conformation of the condylar cartilage, while resin-embedded and metallographically polished specimens were evaluated through reflection FTIR microscopy to identify mineralization status of the corresponding condylar bone. RESULTS The multivariable analysis revealed significantly lower a-helix to amide I percentage area ratio for the transgenic animals after adjusting for diet (β=-4.29, 95% CIs: -8.52, -0.06; p=0.04). Mineral phase indices did not differ significantly between RA and control groups regardless the type of diet. CONCLUSIONS Internal derangement of the anatomical structure with denaturation in the collagen structural components of the mandibular condyles of the RA animals was found, while no association with functional loading through diet modification was recorded.
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Affiliation(s)
- Despina Koletsi
- Department of Orthodontics, School of Dentistry, University of Athens, Thivon 2, 11527 Goudi, Athens, Greece; Endowed Chair of Oral Technology, School of Dentistry, University of Bonn, Welschnonnenstraβe 17, 53111 Bonn, Germany
| | - Theodore Eliades
- Clinic of Orthodontics and Paediatric Dentistry, Center of Dental Medicine, University of Zurich, Plattenstrasse 11, CH-8032 Zurich, Switzerland.
| | - Spiros Zinelis
- Clinic of Orthodontics and Paediatric Dentistry, Center of Dental Medicine, University of Zurich, Plattenstrasse 11, CH-8032 Zurich, Switzerland; Department of Dental Biomaterials, School of Dentistry, University of Athens, Thivon 2, 11527 Goudi, Athens, Greece
| | - Margarita Makou
- Department of Orthodontics, School of Dentistry, University of Athens, Thivon 2, 11527 Goudi, Athens, Greece
| | - Christoph Bourauel
- Endowed Chair of Oral Technology, School of Dentistry, University of Bonn, Welschnonnenstraβe 17, 53111 Bonn, Germany
| | - George Eliades
- Department of Dental Biomaterials, School of Dentistry, University of Athens, Thivon 2, 11527 Goudi, Athens, Greece
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Figueroba S, Desjardins M, Nani B, Ferreira L, Rossi A, Santos F, Venâncio P, Aguiar F, Groppo F. Effect of diazepam on temporomandibular joints in rats with increased occlusal vertical dimension. Br J Oral Maxillofac Surg 2014; 52:438-44. [DOI: 10.1016/j.bjoms.2014.02.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 02/12/2014] [Indexed: 10/25/2022]
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Mandibular asymmetry: a three-dimensional quantification of bilateral condyles. Head Face Med 2013; 9:42. [PMID: 24354862 PMCID: PMC3878129 DOI: 10.1186/1746-160x-9-42] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2013] [Accepted: 12/17/2013] [Indexed: 11/10/2022] Open
Abstract
INTRODUCTION The shape and volume of the condyle is considered to play an important role in the pathogenesis of the mandibular deviation. Curvature analysis is informative for objectively assess whether the shape of the condyles matches that of the glenoid fossa. In this study, a three-dimensional (3-D) quantification of bilateral asymmetrical condyles was firstly conducted to identify the specific role of 3-D condylar configuration for mandibular asymmetry. METHODS 55 adult patients, 26 males (26 ± 5 yrs) and 29 females (26 ± 5 yrs), diagnosed with mandibular asymmetry were included. The examination of deviation of chin point, deviation of dental midlines, inclination of occlusal plane, and depth of the mandibular occlusal plane were conducted. After the clinical investigation, computed tomography images from the patients were used to reconstruct the 3-D mandibular models. Then the condylar volume, surface size, surface curvature and bone mineral density were evaluated independently for each patient on non-deviated and deviated sides of temporomandibular joint. RESULTS Both the condylar surface size and volume were significantly larger on deviated side (surface size: 1666.14 ± 318.3 mm2, volume: 1981.5 ± 418.3 mm3). The anterior slope of the condyle was flatter (0.12 ± 0.06) and the posterior slope (0.39 ± 0.08) was prominently convex on the deviated side. The corresponding bone mineral density values were 523.01 ±118.1 HU and 549.07 ±120. 6 HU on anterior and posterior slopes. CONCLUSIONS The incongruence presented on the deviated side resulted in a reduction in contact areas and, thus, an increase in contact stresses and changes of bone density. All aforementioned results suggest that the difference existing between deviated and non-deviated condyles correlates with facial asymmetrical development. In mandibular asymmetry patients, the 3-D morphology of condyle on deviated side differ from the non-deviated side, which indicates the association between asymmetrical jaw function and joint remodeling.
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Ho LJ, Hung LF, Liu FC, Hou TY, Lin LC, Huang CY, Lai JH. Ginkgo biloba extract individually inhibits JNK activation and induces c-Jun degradation in human chondrocytes: potential therapeutics for osteoarthritis. PLoS One 2013; 8:e82033. [PMID: 24349175 PMCID: PMC3859542 DOI: 10.1371/journal.pone.0082033] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Accepted: 10/20/2013] [Indexed: 12/15/2022] Open
Abstract
Osteoarthritis (OA) is a common joint disorder with varying degrees of inflammation. The ideal anti-OA drug should have immunomodulatory effects while at the same time having limited or no toxicity. We examined the anti-inflammatory effects of Ginkgo biloba extract (EGb) in interleukin-1 (IL-1)-stimulated human chondrocytes. Chondrocytes were prepared from cartilage specimens taken from patients with osteoarthritis who had received total hip or total knee replacement. The concentrations of chemokines and the degree of cell migration were determined by ELISA and chemotaxis assays, respectively. The activation of inducible nitric oxide synthase (iNOS), mitogen-activated protein kinases (MAPKs), activator protein-1 (AP-1), and nuclear factor-kappaB (NF-κB) was determined by immunoblotting, immunohistochemistry, and electrophoretic mobility shift assay. We found that EGb inhibited IL-1-induced production of chemokines, which in turn resulted in attenuation of THP-1 cell migration toward EGb-treated cell culture medium. EGb also suppressed IL-1-stimulated iNOS expression and release of nitric oxide (NO). The EGb-mediated suppression of the iNOS-NO pathway correlated with the attenuation of activator protein-1 (AP-1) but not nuclear factor-kappaB (NF-κB) DNA-binding activity. Of the mitogen-activated protein kinases (MAPKs), EGb inhibited only c-Jun N-terminal kinase (JNK). Unexpectedly, EGb selectively caused degradation of c-Jun protein. Further investigation revealed that EGb-mediated c-Jun degradation was preceded by ubiquitination of c-Jun and could be prevented by the proteosome inhibitor MG-132. The results imply that EGb protects against chondrocyte degeneration by inhibiting JNK activation and inducing ubiquitination-dependent c-Jun degradation. Although additional research is needed, our results suggest that EGb is a potential therapeutic agent for the treatment of OA.
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Affiliation(s)
- Ling-Jun Ho
- Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan, R.O.C.
- Graduate Institute of Basic Medical Science, PhD Program of Aging, China Medical University, Taichung, Taiwan, R.O.C.
| | - Li-Feng Hung
- Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan, R.O.C.
| | - Feng-Cheng Liu
- Rheumatology/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
| | - Tsung-Yun Hou
- Rheumatology/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
| | - Leou-Chyr Lin
- Department of Orthopaedics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
| | - Chuan-Yueh Huang
- Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan, R.O.C.
| | - Jenn-Haung Lai
- Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, R.O.C.
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan, R.O.C.
- * E-mail:
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15
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Ha MH, Kim YI, Park SB, Kim SS, Son WS. Cone-beam computed tomographic evaluation of the condylar remodeling occurring after mandibular set-back by bilateral sagittal split ramus osteotomy and rigid fixation. Korean J Orthod 2013; 43:263-70. [PMID: 24396735 PMCID: PMC3879282 DOI: 10.4041/kjod.2013.43.6.263] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2013] [Revised: 07/03/2013] [Accepted: 07/04/2013] [Indexed: 11/14/2022] Open
Abstract
Objective To evaluate condylar head remodeling after mandibular set-back sagittal split ramus osteotomy (SSRO) with rigid fixation in skeletal class III deformities. The correlation between condylar head remodeling and condylar axis changes was determined using cone-beam computed tomography (CBCT) superimposition. Methods The CBCT data of 22 subjects (9 men and 13 women) who had undergone mandibular set-back SSRO with rigid fixation were analyzed. Changes in the condylar head measurements and the distribution of the signs of condylar head remodeling were evaluated by CBCT superimposition. Results The subjects showed inward rotation of the axial condylar angle; reduced condylar heights on the sagittal and coronal planes; and resorptive remodeling in the anterior and superior areas on the sagittal plane, superior and lateral areas on the coronal plane, and anterior-middle and anterior-lateral areas on the axial plane (p < 0.05). Conclusions The CBCT superimposition method showed condylar head remodeling after mandibular set-back SSRO with rigid fixation. In skeletal class III patients, SSRO with rigid fixation resulted in rotation, diminution, and remodeling of the condylar head. However, these changes did not produce clinical signs or symptoms of temporomandibular disorders.
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Affiliation(s)
- Man-Hee Ha
- Department of Orthodontics, School of Dentistry, Pusan National University, Yangsan, Korea
| | - Yong-Il Kim
- Department of Orthodontics, School of Dentistry, Pusan National University, Yangsan, Korea. ; Biomedical Research Institute, Pusan National University Hospital, Busan, Korea. ; Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Korea
| | - Soo-Byung Park
- Department of Orthodontics, School of Dentistry, Pusan National University, Yangsan, Korea
| | - Seong-Sik Kim
- Department of Orthodontics, School of Dentistry, Pusan National University, Yangsan, Korea
| | - Woo-Sung Son
- Department of Orthodontics, School of Dentistry, Pusan National University, Yangsan, Korea
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Spyropoulou A, Basdra EK. Mechanotransduction in bone: Intervening in health and disease. World J Exp Med 2013; 3:74-86. [DOI: 10.5493/wjem.v3.i4.74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Revised: 09/06/2013] [Accepted: 11/03/2013] [Indexed: 02/06/2023] Open
Abstract
Mechanotransduction has been proven to be one of the most significant variables in bone remodeling and its alterations have been shown to result in a variety of bone diseases. Osteoporosis, Paget’s disease, orthopedic disorders, osteopetrosis as well as hyperparathyroidism and hyperthyroidism all comprise conditions which have been linked with deregulated bone remodeling. Although the significance of mechanotransduction for bone health and disease is unquestionable, the mechanisms behind this important process have not been fully understood. This review will discuss the molecules that have been found to be implicated in mechanotransduction, as well as the mechanisms underlying bone health and disease, emphasizing on what is already known as well as new molecules potentially taking part in conveying mechanical signals from the cell surface towards the nucleus under physiological or pathologic conditions. It will also focus on the model systems currently used in mechanotransduction studies, like osteoblast-like cells as well as three-dimensional constructs and their applications among others. It will also examine the role of mechanostimulatory techniques in preventing and treating bone degenerative diseases and consider their applications in osteoporosis, craniofacial development, skeletal deregulations, fracture treatment, neurologic injuries following stroke or spinal cord injury, dentistry, hearing problems and bone implant integration in the near future.
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Seo KW, Lee SJ, Kim YH, Bae JU, Park SY, Bae SS, Kim CD. Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway. PLoS One 2013; 8:e70437. [PMID: 23950935 PMCID: PMC3737227 DOI: 10.1371/journal.pone.0070437] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2013] [Accepted: 06/18/2013] [Indexed: 12/21/2022] Open
Abstract
Increased blood pressure, leading to mechanical stress on vascular smooth muscle cells (VSMC), is a known risk factor for vascular remodeling via increased activity of matrix metalloproteinase (MMP) within the vascular wall. This study aimed to identify cell surface mechanoreceptors and intracellular signaling pathways that influence VSMC to produce MMP in response to mechanical stretch (MS). When VSMC was stimulated with MS (0–10% strain, 60 cycles/min), both production and gelatinolytic activity of MMP-2, but not MMP-9, were increased in a force-dependent manner. MS-enhanced MMP-2 expression and activity were inhibited by molecular inhibition of Akt using Akt siRNA as well as by PI3K/Akt inhibitors, LY293002 and AI, but not by MAPK inhibitors such as PD98059, SP600125 and SB203580. MS also increased Akt phosphorylation in VSMC, which was attenuated by AG1295, a PDGF receptor (PDGFR) inhibitor, but not by inhibitors for other receptor tyrosine kinase including EGF, IGF, and FGF receptors. Although MS activated PDGFR-α as well as PDGFR-β in VSMC, MS-induced Akt phosphorylation was inhibited by molecular deletion of PDGFR-β using siRNA, but not by inhibition of PDGFR-α. Collectively, our data indicate that MS induces MMP-2 production in VSMC via activation of Akt pathway, that is mediated by activation of PDGFR-β signaling pathways.
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MESH Headings
- Animals
- Cells, Cultured
- Gene Expression
- Immunoblotting
- Immunohistochemistry
- Matrix Metalloproteinase 2/genetics
- Matrix Metalloproteinase 2/metabolism
- Microscopy, Confocal
- Muscle, Smooth, Vascular/cytology
- Muscle, Smooth, Vascular/metabolism
- Myocytes, Smooth Muscle/cytology
- Myocytes, Smooth Muscle/metabolism
- Phosphorylation
- Proto-Oncogene Proteins c-akt/antagonists & inhibitors
- Proto-Oncogene Proteins c-akt/genetics
- Proto-Oncogene Proteins c-akt/metabolism
- RNA Interference
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species/metabolism
- Receptor, Platelet-Derived Growth Factor beta/antagonists & inhibitors
- Receptor, Platelet-Derived Growth Factor beta/genetics
- Receptor, Platelet-Derived Growth Factor beta/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
- Stress, Mechanical
- Tyrphostins/pharmacology
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Affiliation(s)
- Kyo Won Seo
- Department of Pharmacology, School of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
| | - Seung Jin Lee
- Department of Pharmacology, School of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
| | - Yun Hak Kim
- Department of Pharmacology, School of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
| | - Jin Ung Bae
- Department of Pharmacology, School of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
| | - So Youn Park
- Department of Pharmacology, School of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
| | - Sun Sik Bae
- Department of Pharmacology, School of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
| | - Chi Dae Kim
- Department of Pharmacology, School of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Gyeongnam, Republic of Korea
- * E-mail:
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Lau KHW, Baylink DJ, Zhou XD, Rodriguez D, Bonewald LF, Li Z, Ruffoni D, Müller R, Kesavan C, Sheng MHC. Osteocyte-derived insulin-like growth factor I is essential for determining bone mechanosensitivity. Am J Physiol Endocrinol Metab 2013; 305:E271-81. [PMID: 23715728 DOI: 10.1152/ajpendo.00092.2013] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This study sought to determine whether deficient Igf1 expression in osteocytes would affect loading-induced osteogenic response. Tibias of osteocyte Igf1 conditional knockout (KO) mice (generated by cross-breeding Igf1 floxed mice with Dmp1-Cre transgenic mice) and wild-type (WT) littermates were subjected to four-point bending for 2 wk. Microcomputed tomography confirmed that the size of tibias of conditional mutants was smaller. Loading with an equivalent loading strain increased periosteal woven bone and endosteal lamellar bone formation in WT mice but not in conditional KO mice. Consistent with the lack of an osteogenic response, the loading failed to upregulate expression of early mechanoresponsive genes (Igf1, Cox-2, c-fos) or osteogenic genes (Cbfa-1, and osteocalcin) in conditional KO bones. The lack of osteogenic response was not due to reduced osteocyte density or insufficient loading strain. Deficient osteocyte Igf1 expression reduced the loading-induced upregulation of expression of canonical Wnt signaling genes (Wnt10b, Lrp5, Dkk1, sFrp2). The loading also reduced (by 40%) Sost expression in WT mice, but the loading not only did not reduce but upregulated (~1.5-fold) Sost expression in conditional KO mice. Conditional disruption of Igf1 in osteocytes also abolished the loading-induced increase in the bone β-catenin protein level. These findings suggest an impaired response in the loading-induced upregulation of the Wnt signaling in conditional KO mice. In summary, conditional disruption of Igf1 in osteocytes abolished the loading-induced activation of the Wnt signaling and the corresponding osteogenic response. In conclusion, osteocyte-derived IGF-I plays a key determining role in bone mechanosensitivity.
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Affiliation(s)
- K-H William Lau
- Division of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA
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Psychological stress alters microstructure of the mandibular condyle in rats. Physiol Behav 2013; 110-111:129-39. [PMID: 23313405 DOI: 10.1016/j.physbeh.2013.01.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2012] [Revised: 01/02/2013] [Accepted: 01/06/2013] [Indexed: 11/21/2022]
Abstract
Psychological stress plays an important role in the occurrence and development of temporomandibular joint disorder (TMD). The correlation between psychological factors and TMD has been clinically shown, but the influence of psychological stress on the temporomandibular joint (TMJ) structure still lacks direct evidence. Here, we used communication box to establish the rat model of psychological stress. The stress level of animals was estimated by the elevated plus maze (EPM) test and hormonal assays. The histomorphology and three-dimensional microstructure of the rat condyles were observed by hematoxylin-eosin (HE) staining and Micro-CT, respectively. Compared with control rats, the anxious state of the stressed rats was evidenced by higher plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT), as well as lower ratios of open arm entries and time and lower time spent in open arms after 1, 2, 3, 4 and 5 week(s) post-exposure to psychological stimuli. HE staining and histomorphometric data analysis showed decreased thicknesses of the central and posterior condylar cartilages in stressed rats at weeks 3, 4 and 5, with the most obvious changes in the posterior part characterized by debonding and thinned fibrous layer, thickened proliferative layer, thinned mature layer and hypertrophic layer. Moreover, Micro-CT scanning revealed local lesion of the subchondral bone in the posterior condylar cartilages of stressed rats at week 5. Our findings indicate that pathologic changes of the histomorphology and three-dimensional microstructure occur in the condyles of stressed rats, hinting us a potential link between psychological factors and the pathogenesis or progression of TMD.
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