Distinct Responses of Estrogen Receptor α and β in Chondrocytes Under Excessive Mechanical Stress.

IntroductionOsteoarthritis (OA) is more common in women, suggesting a link to estrogen. Estrogen supports cartilage homeostasis and metabolism via two receptors: ERα and ERβ. Mechanical stress is the primary cause of OA and affects cellular functions, including receptor activity. The link between excessive mechanical stress and ERs in cartilage is poorly understood. This study examined ER expression changes in chondrocytes under mechanical stress and the role of estrogen in cartilage degradation and ER regulation.MethodsATDC5 chondrocytes were treated with 17β-estradiol (E2; 1.0 × 10⁻⁷M) and subjected to cyclic tensile strain using the Flexcell Tension Plus FX-2000. Total RNA and proteins were extracted, and IL-1β and MMP-13 expression were analyzed using RT-PCR and western blotting. RT-PCR was used to examine the expression of ERα and ERβ.ResultsThe CTS group had significantly downregulated ERα expression at all time points and upregulated ERβ expression after 3 and 6 hours compared with controls. In the E2+CTS group, IL-1β and MMP-13 expression were suppressed after 3 and 6 hours, coinciding with significant upregulation of ERβ compared with the CTS group.ConclusionsEstrogen exerts a chondroprotective effect under excessive mechanical stress, suggesting that ERβ mediates this effect.