The adaptive response of the mandibular condyle to increased load is disrupted by ADAMTS5 deficiency

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.