Estrogen via estrogen receptor beta partially inhibits mandibular condylar cartilage growth.

OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role for female hormones in the disease process. However, little is known about the role of estrogen receptor (ER) signaling in regulating mandibular condylar cartilage growth. Therefore, the goal of this study was to examine the effects of altered estrogen levels on the mandibular condylar cartilage in wild type (WT) and ER beta Knockout (KO) mice. MATERIALS AND METHODS: 21-day-old female WT (n = 37) and ER beta KO mice (n = 36) were either sham operated or ovariectomized, and treated with either placebo or estradiol. The mandibular condylar cartilage was evaluated by histomorphometry, proliferation was analyzed by double ethynyl-2'-deoxyuridine/bromodeoxyuridine (EdU/BrdU) labeling, and assays on gene and protein expression of chondrocyte maturation markers were performed. RESULTS: In WT mice, ovariectomy caused a significant increase in mandibular condylar cartilage cell numbers, a significant increase in Sox9 expression and a significant increase in proliferation compared with sham operated WT mice. In contrast, ovariectomy did not cause any of these effects in the ER beta KO mice. Estrogen replacement treatment in ovariectomized WT mice caused a significant decrease in ER alpha expression and a significant increase in Sost expression compared with ovariectomized mice treated with placebo. Estrogen replacement treatment in ovariectomized ER beta KO mice caused a significant increase in Col2 expression, no change in ER alpha expression, and a significant increase in Sost expression. CONCLUSION: Estrogen via ER beta inhibits proliferation and ER alpha expression while estrogen independent of ER beta induces Col2 and Sost expression.

Early-onset osteoarthritis of mouse temporomandibular joint induced by partial discectomy.

OBJECTIVE: The objective of this study is to characterize mouse temporomandibular joint (TMJ) following partial discectomy, since there is no documentation of whether or not partial discectomy can induce early-onset osteoarthritis (OA) in mouse TMJ. METHODS: Partial discs of TMJ in mice were removed by microsurgery. Histology was performed to characterize articular cartilages from the TMJ of mice. The morphology of the articular cartilages was evaluated using a modified Mankin scoring system. Immunohistostaining was carried out to examine the expression of discoidin domain receptor 2 (Ddr2), a type II collagen receptor, matrix metalloproteinase-13 (Mmp-13), and Mmp-derived type II collagen fragments in the articular cartilage of condyles from the mouse TMJ. RESULTS: Articular cartilage degeneration was seen in the mouse TMJ post-discectomy, including increased proteoglycan staining in the extracellular matrix at 4 weeks, the appearance of chondrocyte clusters at 8 weeks, reduced proteoglycan staining and fibrillation at 12 weeks and the loss of articular cartilage at 16 weeks. Increased immunostaining for Ddr2, Mmp-13, and Mmp-derived type II collagen fragments was detected. CONCLUSION: Results indicate that partial discectomy induces early-onset OA in mouse TMJ and that increased expression of Mmp-13, likely due to the elevated expression of Ddr2, may be one of the factors responsible for the early-onset OA in mouse TMJ.