Estrogen Induces Apoptosis in Mammalian Growth Plate Chondrocytes via ERα36-dependent Signaling

Endochondral ossification occurs when chondrocytes proliferate, differentiate, hypertrophy and eventually undergo apoptosis. Multiple systemic and local stimuli orchestrate to regulate this process, among which estrogen is one key factor. Estrogen induces the pubertal growth spurt, but later causes epiphyseal fusion terminating the endochondral ossification process. The effect of estrogen on endochondral bone formation is strictly determined by its concentration, since both excessive and deficient estrogen cause diminished bone growth. We have established an in vitro culture system of rat costochondral growth plate chondrocytes to study the effect of estrogen on the regulation of cell proliferation, differentiation and apoptosis. In our current study, we concentrate on the resting zone since it is the source of cells in the longitudinal columns of growth plate. Previously, we have shown that estrogen inhibits cell proliferation whereas it increases differentiation in resting zone chondrocytes, via a membrane receptor pathway that involves protein kinase C (PKC) activation. The purpose of our current study was to determine whether estrogen also controls their apoptosis, and to identify the signaling pathway involved.