title: Overexpressed TGF-β in subchondral bone leads to mandibular condyle degradation.
abstract: Emerging evidence has implied that subchondral bone plays an important role during osteoarthritis (OA) pathology. This study was undertaken to investigate whether abnormalities of the condylar subchondral bone lead to temporomandibular joint (TMJ) OA. We used an osteoblast-specific mutant TGF-β1 transgenic mouse, the CED mouse, in which high levels of active TGF-β1 occur in bone marrow, leading to abnormal bone remodeling. Subchondral bone changes in the mandibular condyles were investigated by micro-CT, and alterations in TMJ condyles were confirmed by histopathological and immunohistochemical analysis. Abnormalities in the condylar subchondral bone, characterized as fluctuant bone mineral density and microstructure and increased but uncoupled activity of osteoclasts and osteoblasts, were apparent in the 1- and 4-month CED mouse groups, while obvious cartilage degradation, in the form of cell-free regions and proteoglycan loss, was observed in the 4-month CED group. In addition, increased numbers of apoptotic chondrocytes and MMP9- and VEGF-positive chondrocytes were observed in the condylar cartilage in the 4-month CED group, but not in the 1-month CED group, compared with their respective age-matched controls. This study demonstrated that progressive degradation of mandibular condylar cartilage could be induced by the abnormal remodeling of the underlying subchondral bone during TMJOA progression.
authors.affiliation: Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, 145 Changlexi Road, Xi'an, 710032, China.
authors.forename: K
authors.initials: K
authors.lastname: Jiao
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Niu
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.forename: G
authors.initials: G
authors.lastname: Zhen
authors.forename: L
authors.initials: L
authors.lastname: Xian
authors.forename: B
authors.initials: B
authors.lastname: Yu
authors.forename: K
authors.initials: K
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Cao
authors.forename: M
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015519:Bone Density / Q000502:physiology; D001853:Bone Marrow / Q000473:pathology; D016723:Bone Remodeling / Q000235:genetics; D002356:Cartilage / Q000473:pathology; D016022:Case-Control Studies; D053148:Caspase 3 / Q000032:analysis; D019902:Chondrocytes / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D008335:Mandibular Condyle / Q000473:pathology*; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000235:genetics*; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis; D013705:Temporomandibular Joint Disorders / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D024042:Collagen Type I; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D053148:Caspase 3; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Micro-CT; cartilage; osteoarthritis; subchondral bone; temporomandibular joint; transgenic mouse