Despite using an overexpression system, our data suggest that in a pathological situation that leads to high levels of expressed and active HRAS, osteogenic signaling may be impaired by changes in the Runx2 and Opn expression, and bone pathophenotype in CS and other RASopathies may be amenable to inhibitors of RAS farnesylation. The gene discussed is HRAS; the disease is RASopathy.