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

Connect Tissue Res. 2023 Jan;64(1):93-104. doi: 10.1080/03008207.2022.2102491. Epub 2022 Aug 1.

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.

Keywords: extracellular matrix, adamts5, mandibular condyle; matrix biology; matrix metalloproteinases; temporomandibular joint (tmj).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS5 Protein
  • Animals
  • Cartilage
  • Extracellular Matrix
  • Mandibular Condyle*
  • Mechanotransduction, Cellular*
  • Mice
  • Temporomandibular Joint

Substances

  • Adamts5 protein, mouse
  • ADAMTS5 Protein