FSH directly regulates chondrocyte dedifferentiation and cartilage development

in Journal of Endocrinology
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  • 1 Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
  • 2 Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong Province, China
  • 3 Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
  • 4 Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China
  • 5 Department of Endocrinology, Taian City Central Hospital, Taian, Shandong Province, China

Correspondence should be addressed to J Xu: xujin267903@163.com
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Previous studies suggest that postmenopausal osteoarthritis is linked to a decrease in estrogen levels. However, whether follicle-stimulating hormone (FSH), the upstream hormone of estrogen, affects cartilage destruction and thus contributes to the onset of osteoarthritis has never been explored. To evaluate the potential involvement of FSH in joint degeneration and to identify the molecular mechanisms through which FSH influences chondrocytes, mouse cartilage chondrocytes and the ATDC5 chondrocyte cell line were treated with FSH and inhibitors of intracellular signaling pathways. We observed that FSH induces chondrocyte dedifferentiation by decreasing type II collagen (Coll-II) synthesis. Chondrocyte cytoskeleton reorganization was also observed after FSH treatment. The FSH-induced decrease in Coll-II was rescued by ERK-1/2 inhibition but aggravated by p38 inhibition. In addition, knocking down the FSH receptor (Fshr) by using Fshr siRNA abolished chondrocyte dedifferentiation, as indicated by the increased expression of Coll-II. Inhibition of the protein Gαi by pertussis toxin (PTX) also restored FSH-inhibited Coll-II, suggesting that Gαi is downstream of FSHR in chondrocyte dedifferentiation. FSHβ antibody blockade prevented cartilage destruction and cell loss in mice. Moreover, decreased Coll-II staining due to the progression of aging could be rescued by blocking FSH. Thus, we suggest that high circulating FSH, independent of estrogen, is an important regulator in chondrocyte dedifferentiation and cartilage destruction.

 

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