title: 1,25(OH)2D deficiency induces temporomandibular joint osteoarthritis via secretion of senescence-associated inflammatory cytokines.
abstract: 1,25-Dihydroxyvitamin D [1,25(OH)(2)D] insufficiency appears to be associated with several age-related diseases. Insufficient levels of serum 25-hydroxyvitamin D has been shown to lead to the progression of osteoarthritis (OA) while underlying biological mechanisms remain largely unknown. In this study, we sought to determine whether 1,25(OH)(2)D deficiency has a direct effect on the process of murine temporomandibular joint (TMJ) OA in 25-hydroxyvitamin D 1α-hydroxylase knockout [1α(OH)ase(-/-)] mice that had been fed a rescue diet (high calcium, phosphate, and lactose) from weaning until 6 or 18 months of age. Our results showed that the bone mineral density and subchondral bone volume were reduced in mandibular condyles, articular surfaces were collapsed, the thickness of articular cartilage and cartilage matrix protein abundance were progressively decreased and eventually led to an erosion of articular cartilage of mandibular condyles. We also found that DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were increased significantly in 1α(OH)ase(-/-) mice. This study demonstrates that 1,25(OH)(2)D deficiency causes an erosive TMJ OA phenotype by inducing DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines. Our results indicate that 1,25(OH)(2)D plays an important role in preventing the development and progression of OA.
authors.affiliation: Institute of Stomatology, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing 210029, Jiangsu, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Luo
authors.forename: Yuming
authors.initials: Y
authors.lastname: Niu
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Yuan
authors.forename: David
authors.initials: D
authors.lastname: Goltzman
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000172:deficiency / Q000235:genetics; D000818:Animals; D015519:Bone Density / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D013704:Temporomandibular Joint / Q000378:metabolism / Q000473:pathology; D013705:Temporomandibular Joint Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014808:Vitamin D Deficiency / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D016207:Cytokines; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase