Abstract
OBJECTIVE: To determine the impact of increased load on the temporomandibular joint (TMJ) from mice deficient in the extracellular matrix protease ADAMTS5. MATERIALS AND METHODS: Wire springs exerting 0.5 N for 1 h/day for 5 days (Adamts5(+/+) -n = 18; Adamts5(-/-) n = 19) or 0.8 N for 1 h/day for 10 days (Adamts5(+/+)-n = 18; Adamts5(-/-) n = 17) were used to increase murine TMJ load. Safranin O-staining was used to determine mandibular condylar cartilage (MCC) morphology. Chondrogenic factors Sox9 and aggrecan were immunolocalized. Microcomputed topography was employed to evaluate mineralized tissues, and Tartrate-Resistant Acid Phosphatase staining was used to quantify osteoclasts. RESULTS: Increased load on the mandibular condyle of Adamts5(-/-) mice resulted in an increase in the hypertrophic zone of mandibular condylar cartilage (MCC) compared to normal load (NL) (P < 0.01). In the trabecular bone of the mandibular condyle, the total volume (TV), bone volume (BV), trabecular thickness (TbTh), and trabecular separation (TbSp) of the mandibular condyles in Adamts5(-/-) mice (n = 27) did not change significantly with increased load, compared to Adamts5(+/+) (n = 38) that exhibited significant responses (TV-P < 0.05; BV-P < 0.001; TbTh-P < 0.01; TbSp-P < 0.01). The bone volume fraction (BV/TV) was significantly reduced in response to increased load in both Adamts5(-/-) (P < 0.05) and Adamts5(+/+) mandibular condyles (P < 0.001) compared to NL. Increased load in Adamts5(-/-) mandibular condyles also resulted in a dramatic increase in osteoclasts compared to Adamts5(-/-) NL (P < 0.001) and to Adamts5(+/+) with increased load (P < 01). CONCLUSION: The trabeculated bone of the Adamts5(-/-) mandibular condyle was significantly less responsive to the increased load compared to Adamts5(+/+). ADAMTS5 may be required for mechanotransduction in the trabeculated bone of the mandibular condyle.