MC-GAG induces osteogenic differentiation of primary hMSCs via an autogenous activation of the canonical BMPR signaling pathway with phosphorylation of Smad1/5/8 (Mechanism 1, green arrow). MC-GAG directly inhibits viability, proliferation, and resorptive activity of osteoclasts even in the absence of differentiating hMSCs (Mechanism 2A, red lines). MC-GAG also upregulates OPG expression through an ERK1/2 dependent pathway, correlating to an indirect inhibition of resorptive activity but not viability or proliferation in co-culture with differentiating hMSCs (Mechanism 2B, red arrows and lines).