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^-/0fmod^-/-). Differential gene expression analysis was performed with RNA extracted from 3-week-old WT and bgn^-/0fmod^-/- TMJs with an intact cartilage/subchondral bone interface. In total, 22 genes were differentially expressed in bgn^-/0fmod^-/- TMJs, including 5 genes involved in osteoclast activity/differentiation. The number of TRAP-positive cells were three-fold higher in bgn^-/0fmod^-/- TMJs than in WT. Quantitative RT-PCR showed up-regulation of RANKL and OPG, with a 128% increase in RANKL/OPG ratio in bgn^-/0fmod^-/- TMJs. Histology and immunohistochemistry revealed tissue disorganization and reduced type I collagen in bgn^-/0fmod^-/- TMJ subchondral bone. Early changes in gene expression and tissue defects in young bgn^-/0fmod^-/- 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.

Keywords

temporomandibular disorders osteoclasts matrix biology bone biology osteoarthritis cartilage

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