An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage

Objective To review cellular mechanisms that have been proposed to mediate the indirect and direct effects of estrogen on articular cartilage, and to outline the remaining clinical questions that need to be clarified before utilizing the beneficial effects of estrogen for the prevention of osteoarthritis in early postmenopausal women. Design Summary of original research papers and reviews listed in Pubmed (1980-2007). Results Estrogen receptors have been identified in articular chondrocytes from various animals and humans. Molecular studies showed that estrogen can elicit genomic and rapid non-genomic effects on various cell types, including chondrocytes, and the latter effects are only inducible in females. In addition to direct effects, estrogen can also affect the homeostasis of articular cartilage by modulating the expression/production of different molecules such as various growth factors, inflammatory cytokines, matrix metalloproteinases, and reactive oxygen species. Moreover, invivo observation argues for the notion that inhibition of subchondral bone turnover is also part of the mechanisms by which estrogen (and antiresorptive agents in general) can protect against joint degradation. Published studies undertaken at cellular, tissue, and invivo levels illustrate that the effect of estrogen on cartilage may depend on the dose applied, the administration route, the time of initiation, and whether it is combined with a progestin. Conclusions The herein reviewed direct and indirect effects of estrogen on articular cartilage further corroborate the due consideration of estrogen therapy for maintaining not only bone but also cartilage health in postmenopausal women. Future studies in postmenopausal women are needed to clarify whether the efficacy of estrogen therapy can be further optimized by using other forms of estrogen, other progestins, or by initiating the therapy in the peri- or early postmenopausal period.