The expression and potential roles of Estrogen Receptor-beta in musculoskeletal diseases

抄録

Background The musculoskeletal diseases such as osteoarthritis (OA) and tendinopathy affect a wide range of individual in the world and are usually female dominant. Alteration of hormone levels and external mechanical stress may mutually affect disease progression. We previously showed that estrogen receptor-beta (ER-beta) expression was higher in patients with de Quervain's disease. The expression of this receptor may associate with these diseases manifestation. How estrogen and mechanical loading modulate the pathogenesis of these diseases remains elusive.

Methods A collagenase I-induced tendinopathy and a surgery-induced OA models in rats were established to examine the association of ER-beta with disease. The tissues were examined by alcian blue stain and micro-CT image analysis. Furthermore, to study the underlying mechanisms, a cyclic stretching culture system was applied to tendon tissues from female rats with oophorectomy. The tissues were examined by immunochemical, immunofluorescence staining, and TUNEL assay.

Results Our results showed that the lack of estrogen exacerbated the osteoarthritis and increased the ER-beta expression in the synovium of rats. In addition, the ER-beta and apoptotic cells were highly expressed and related to disease severity in tendon tissues from rats with tendinopathy. The mechanic strain altered the morphology of primary tenocytes and the collagen fiber alignment of tendon tissues, as well as the expression of ER-beta and apoptotic cells in tenocytes and tendon tissues from oophorectomized rats.

Conclusions Our study revealed the potential roles of estrogen and mechanical loading, through ERs, in OA and tendinopathy. These findings suggest that the musculoskeletal disorders shared some common pathogenic process. It may contribute to the development of pharmacological therapies targeting ER-beta signaling pathways for the treatment of these diseases.