IADR Abstract Archives
Estrogen and Relaxin Mediate Targeted Increase in TMJ Subchondral Bone Porosity That Requires MMP9 and MMP13
Objectives: We have previously shown that estrogen and relaxin contribute to the degradation of TMJ disc fibrocartilage by inducing specific matrix metalloproteinases (MMPs). In this study we determined the effects of these hormones on TMJ subchondral bone phenotype, compared them with those of similar sites in long bones and determined the contribution of MMP9 and MMP13 to these changes.
Methods: Osmotic pumps containing estrogen or relaxin or progesterone or PBS were implanted subcutaneously two days following ovariectomies on 12-week-old female C57BL/6 wildtype (WT), MMP9- and MMP13-null mice. After four weeks, the mice were euthanized and the TMJs and femurs retrieved for micro-CT and histologic analyses.
Results: Estrogen and relaxin but not progesterone caused significant increase in TMJ condylar subchondral bone porosity by about 80% and 60%, respectively. Relaxin treatment in the absence of MMP9 and MMP13 did not contribute to increased bone porosity, whereas estrogen caused an increase in porosity in MMP9-null mice similar to that in WT mice but not in MMP13-null mice. None of the hormones caused any adverse changes in the articular subchondral bone or subepiphyseal trabecular bone of the femur. Indeed, the latter site displayed the characteristic effects of estrogen of increased bone deposition. Initial TMJ histology showed decreased total fibrocartilage and hypertrophic chondrocyte layers in condyles from relaxin- and estrogen-treated mice. Additionally, as opposed to the known effects of estrogen on osteoclasts, the osteochondral junction and surfaces of mineralized spicules were heavily stained for TRAP-positive multinucleated cells, presumably osteo/chondroclasts. Consistent with relaxin’s known effects in increasing osteoclast differentiation, relaxin-treated mice showed increased subchondral osteo/chondroclasts but these were fewer than those observed with estrogen.
Conclusions: Estrogen and relaxin specifically compromise the integrity of TMJ condylar subchondral bone possibly through enhanced matrix degradation, perturbed chondrogenesis and increased osteo/chondroclastic activity that requires MMP9 or MMP13 or both proteinases.
Methods: Osmotic pumps containing estrogen or relaxin or progesterone or PBS were implanted subcutaneously two days following ovariectomies on 12-week-old female C57BL/6 wildtype (WT), MMP9- and MMP13-null mice. After four weeks, the mice were euthanized and the TMJs and femurs retrieved for micro-CT and histologic analyses.
Results: Estrogen and relaxin but not progesterone caused significant increase in TMJ condylar subchondral bone porosity by about 80% and 60%, respectively. Relaxin treatment in the absence of MMP9 and MMP13 did not contribute to increased bone porosity, whereas estrogen caused an increase in porosity in MMP9-null mice similar to that in WT mice but not in MMP13-null mice. None of the hormones caused any adverse changes in the articular subchondral bone or subepiphyseal trabecular bone of the femur. Indeed, the latter site displayed the characteristic effects of estrogen of increased bone deposition. Initial TMJ histology showed decreased total fibrocartilage and hypertrophic chondrocyte layers in condyles from relaxin- and estrogen-treated mice. Additionally, as opposed to the known effects of estrogen on osteoclasts, the osteochondral junction and surfaces of mineralized spicules were heavily stained for TRAP-positive multinucleated cells, presumably osteo/chondroclasts. Consistent with relaxin’s known effects in increasing osteoclast differentiation, relaxin-treated mice showed increased subchondral osteo/chondroclasts but these were fewer than those observed with estrogen.
Conclusions: Estrogen and relaxin specifically compromise the integrity of TMJ condylar subchondral bone possibly through enhanced matrix degradation, perturbed chondrogenesis and increased osteo/chondroclastic activity that requires MMP9 or MMP13 or both proteinases.