title: Role of subchondral bone during early-stage experimental TMJ osteoarthritis.
abstract: Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative disease that affects both cartilage and subchondral bone. We used microarray to identify changes in gene expression levels in the TMJ during early stages of the disease, using an established TMJ OA genetic mouse model deficient in 2 extracellular matrix proteins, biglycan and fibromodulin (bgn(-/0)fmod(-/-)). Differential gene expression analysis was performed with RNA extracted from 3-week-old WT and bgn(-/0)fmod(-/-) TMJs with an intact cartilage/subchondral bone interface. In total, 22 genes were differentially expressed in bgn(-/0)fmod(-/-) TMJs, including 5 genes involved in osteoclast activity/differentiation. The number of TRAP-positive cells were three-fold higher in bgn(-/0)fmod(-/-) TMJs than in WT. Quantitative RT-PCR showed up-regulation of RANKL and OPG, with a 128% increase in RANKL/OPG ratio in bgn(-/0)fmod(-/-) TMJs. Histology and immunohistochemistry revealed tissue disorganization and reduced type I collagen in bgn(-/0)fmod(-/-) TMJ subchondral bone. Early changes in gene expression and tissue defects in young bgn(-/0)fmod(-/-) TMJ subchondral bone are likely attributed to increased osteoclast activity. Analysis of these data shows that biglycan and fibromodulin are critical for TMJ subchondral bone integrity and reveal a potential role for TMJ subchondral bone turnover during the initial early stages of TMJ OA disease in this model.
authors.affiliation: Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: M
authors.initials: M
authors.lastname: Embree
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: T
authors.initials: T
authors.lastname: Kilts
authors.forename: D
authors.initials: D
authors.lastname: Walker
authors.forename: J
authors.initials: J
authors.lastname: Langguth
authors.forename: J
authors.initials: J
authors.lastname: Mao
authors.forename: Y
authors.initials: Y
authors.lastname: Bi
authors.forename: J L
authors.initials: JL
authors.lastname: Barth
authors.forename: M
authors.initials: M
authors.lastname: Young
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000503:physiopathology; D058578:Biglycan / Q000172:deficiency / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism / Q000503:physiopathology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000502:physiology*; D000071235:Fibromodulin; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology; D010010:Osteoclasts / Q000378:metabolism; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000235:genetics; D011509:Proteoglycans / Q000172:deficiency / Q000502:physiology*; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013705:Temporomandibular Joint Disorders / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D058578:Biglycan; D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; D053244:Osteoprotegerin; D011509:Proteoglycans; D053245:RANK Ligand; D000071235:Fibromodulin