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

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.