Fig. 9.

Schematic representation of the signalling pathways mediating PTH and BMP-2 induced regulation of Phospho1, Smpd3 and Alpl in osteoblast cells. Recapitulation of the effects of PTH, through the use of the cAMP agonist, forskolin, and inhibition of the effects of PTH through the use of the PKA inhibitor, PKI (5–24) have implicated the cAMP/PKA pathway in mediating the down-regulation of Phospho1 and Smpd3, and the enhancement of Alpl mRNA expression in response to PTH treatment. Initial studies have identified BMP-2 as an inducer of Phospho1, Smpd3 and Alpl expression, although the intracellular signalling pathway is yet to be elucidated. PTH, parathyroid hormone; PTH1R, parathyroid hormone receptor 1; AC, adenylyl cyclase; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; BMP2, bone morphogenic protein 2; BMPR1A, bone morphogenic protein receptor 1A