Progesterone (Pg) and Medroxyprogesterone acetate (MPA) regulate same events with opposite actions in bone and vascular cells

CAMPELO A.; MASSHEIMER V.; CUTINI P.

Congreso; 2020 Annual Meeting of the ASBMR Virtual Event; 2020

Bone and cardiovascular diseases are multifactorial clinical entities that often coexist in postmenopausal women. Clinical and epidemiological studies have shown an interesting relationship between high bone turnover and cardiovascular disease mortality. Disorders in bone metabolism reversely correlate with vascular calcification (VCa). Hormone replacement therapy including natural Pg or synthetic progestins such as MPA emerged as a therapeutic option, although the risk/benefit of its use is controversial. VCa developed within atherosclerotic plaque is partly due to the osteogenic transdifferentiation of vascular smooth muscle cells (VSMC). The aim of this work was to investigate the effect of Pg and MPA on cellular/molecular events involved in VCa and in osteoblastogenesis. Primary cultures of calvarial osteoblasts (OB) and aortic VSMC, were in vitro exposed to 10 nM Pg or 10 nM MPA. Measurements of matrix extracellular calcium content and alkaline phosphatase (ALP) activity were employed as osteoblastic differentiation markers. In order to promote osteoblastic differentiation, VSMC were cultured for 21 days in osteogenic medium (10 mM β-glycerophosphate and 4 mM CaCl2). When VSMC were cultured in osteogenic medium (VSMC-OB), treatment with Pg for 21 days significantly reduced ALP activity (15% below control, p