R-Smads subsequently forms a complex with common Smads (Smad4) and translocate into the nucleus to activate the transcription of target genes such as Runx2 and Alp (Fig. 4b).197 Alternatively, BMP2 signaling can be mediated by the TAK1-p38 kinase pathway.198 BMP2 deficiency in osteoblasts results in osteopenia and bone strength reduction.199. The gene discussed is BMP2; the disease is Osteopenia.