IADR Abstract Archives
Temporomandibular Fibrocartilage Response to ADAMTS5 Deficiency and Mechanical Load
Objectives: Osteoarthritis commonly affects the temporomandibular joint (TMJ) by disrupting extracellular matrix (ECM) homeostasis leading to degradation. The TMJ maintains homeostasis in the mandibular condylar cartilage (MCC) via chemical and mechanical signals. The murine TMJ is responsive to increased static loading by adaptive ECM remodeling and increased chondrocyte maturation. ADAMTS5 is an ECM protease that cleaves aggrecan, a major cartilage proteoglycan. Upregulated ADAMTS5 is a common trademark of osteoarthritis. Our previous research demonstrated that MCC of mice deficient in ADAMTS5 have a polymorphic layer expansion, increase in aggrecan and a decrease of mature hypertrophic cells. Therefore, we hypothesize that ADAMTS5, a morphoregulatory factor, couples ECM architecture with chondrocyte differentiation via aggrecan cleavage in response to mechanical load. The objective was to determine the effect of increased mechanical loading on chondrocyte differentiation in MCC in Adamts5+/+and Adamts5-/- mice.
Methods: Six and a half-week-old Collagen X-mCherry reporter mice on the Adamts5+/+ or Adamts5-/- genetic background were subjected to forced mouth opening with custom springs exerting 0.5N for 1 hr/day for 5 days (n=16/group) or 0.8N for 1 hr/day for 10 days (n=19/group). Controls did not undergo loading. Safranin O/Fast Green, immunohistochemistry, in situ hybridization and qRT-PCR were assessed in loaded and control murine models.
Results: Histology showed increased proteoglycan content and number of hypertrophic chondrocytes with 10 days at 0.8N in both Adamts5+/+ and Adamts5-/- mice, with a more sensitive effect in the deficient model. ColX expression was increased in the hypertrophic layer and subchondral bone in both Adamts5+/+ and Adamts5-/- mice under the extended loading conditions. The expression of aggrecan and other ECM markers were altered in the loaded models.
Conclusions: The MCC of ADAMTS5 deficient mice is responsive to static mechanical load encouraging adaptive remodeling and chondrocyte maturation. We can speculate that other proteases are mechanically activated and unregulated to cleave aggrecan. This study provides new insights into chemical and mechanical mechanisms of TMJ homeostasis and pathophysiologic conditions.
Methods: Six and a half-week-old Collagen X-mCherry reporter mice on the Adamts5+/+ or Adamts5-/- genetic background were subjected to forced mouth opening with custom springs exerting 0.5N for 1 hr/day for 5 days (n=16/group) or 0.8N for 1 hr/day for 10 days (n=19/group). Controls did not undergo loading. Safranin O/Fast Green, immunohistochemistry, in situ hybridization and qRT-PCR were assessed in loaded and control murine models.
Results: Histology showed increased proteoglycan content and number of hypertrophic chondrocytes with 10 days at 0.8N in both Adamts5+/+ and Adamts5-/- mice, with a more sensitive effect in the deficient model. ColX expression was increased in the hypertrophic layer and subchondral bone in both Adamts5+/+ and Adamts5-/- mice under the extended loading conditions. The expression of aggrecan and other ECM markers were altered in the loaded models.
Conclusions: The MCC of ADAMTS5 deficient mice is responsive to static mechanical load encouraging adaptive remodeling and chondrocyte maturation. We can speculate that other proteases are mechanically activated and unregulated to cleave aggrecan. This study provides new insights into chemical and mechanical mechanisms of TMJ homeostasis and pathophysiologic conditions.