Figure 6

Impacts of the binding between BMP2 and IL34 on the ability of BMP2 and IL34 to bind to ACVR2A and MCSFR receptors respectively: importance of stoichiometry and functional consequences on bone formation and resorption. (A) ACVR2A receptor binding to BMP2 (“Wrist” site) does not appear to be affected by IL34 binding to the “Knuckle” sites of a BMP2 dimer. (B) MCSFR receptor binding to IL34 occurs at a site overlapping the BMP2 “Knuckle” site binding site. Simultaneous binding of BMP2 and MCSFR to IL34 is therefore impossible. (C) BMP receptor binding stoichiometry to a BMP2 dimer. The standard binding of two type 1 and two type 2 receptors per dimer (a), is gradually modified by the amount of IL34 present with potential transformation of a “Knuckle” site into a “Wrist”-like site at intermediate concentrations (b), then a second at high IL34 concentrations (c), bearing in mind that IL34 can bind type 2 BMP receptors. (D) Schematic representation of the impact of different ratios of BMPs and IL34 on bone formation and resorption.