title: Subchondral bone loss following orthodontically induced cartilage degradation in the mandibular condyles of rats.
abstract: Osteoarthritis (OA) is a degenerative joint disease generally characterized by progressive cartilage degradation and subchondral bone changes. Subchondral bone changes have been proposed to initiate or accompany with cartilage degradation in OA. The purpose of this study was to characterize cartilage damage, subchondral bone remodeling, and the possible mechanism involved in these morphological changes in our reported rat model with OA-like lesions in the mandibular condyle. In experimental groups, the dental occlusion was orthodontically disturbed. By histological analysis, transmission electron microscopy (TEM), micro-CT scanning and serum tests, changes in condylar cartilage and subchondral bone were analyzed at 8 and 12 weeks after treatment. The mRNA and protein levels of bone pro-resorptive and pro-formative factors by chondrocytes were investigated. Increased degraded cartilage areas and obvious cartilage calcification were observed in 8- and 12-week treated (EXP) groups compared to the age-matched controls. Subchondral bone loss, characterized as decreased bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), but increased trabecular separation (Tb.Sp), was observed in the 12-week but not the 8-week EXP group, respectively, versus their age-matched controls. The subchondral bone loss in the 12-week EXP group was accompanied with decreased new bone formation rate, but increased serum carboxy terminal telopeptides (CTXs), and increased osteoclast numbers and proportion of surface area in the subchondral bone regions. Increased mRNA and protein levels of M-CSF, VEGF, RUNX and RANKL/OPG ratio, but decreased OPG, were found in condylar cartilage in the 12-week EXP group versus its age-matched controls, and those of RANKL/OPG ratios were significantly higher in the 12-week EXP group than the 8-week EXP. In addition, increased mRNA levels of VEGF, RUNX and RANKL/OPG ratio, but decreased OPG, were also found in condylar cartilage in the 8-week EXP group versus its age-matched controls (All P<0.05). This study demonstrated that obvious subchondral bone loss followed cartilage degradation in the mandibular condyles in the present rat models and suggested that the imbalance of chondrocyte-secreted regulatory factors within the degraded cartilage may play a role in the osteoclastogenesis, and thus leading to the subchondral bone loss in OA.
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: Kai
authors.initials: K
authors.lastname: Jiao
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Niu
authors.forename: Mei-Qing
authors.initials: MQ
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Dai
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Yu
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D008335:Mandibular Condyle / Q000378:metabolism* / Q000473:pathology; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley