OPG and RANKL mRNA and protein expressions in the primary and secondary metaphyseal trabecular bone of PTH-treated rats are independent of that of SOST.

Sclerostin, encoded by the SOST gene, is a recently identified protein which seems to affect bone remodeling by inhibiting bone formation via Wnt pathways. A previous study on OPG and RANKL, two cytokines involved in the control of osteoclastogenesis, showed that the anabolic effect produced by intermittent treatment with parathyroid hormone was characterized by an increase in OPG/RANKL mRNA ratio in the primary spongiosa of metaphyseal bone of rat femur, and by its falling in the secondary spongiosa, in comparison to controls (Silvestrini et al. (2007a)). Considering that Wnt pathway components seem to regulate osteoclast formation and bone resorption by repression of RANKL transcription and by positive regulation of OPG gene in osteoblastic cells, we have evaluated, in the same rats, whether and how SOST mRNA and protein in the primary and secondary metaphyseal bone are affected by PTH. SOST mRNA and protein significantly fell in both primary and secondary spongiosa where only a few osteocytes were positive to sclerostin. These data show that in the two metaphyseal areas no relationship does exist between the trends of OPG and RANKL mRNA and that of SOST, suggesting that there are no direct links between the effects induced by PTH on these molecules, at least in terms of gene expression.