The skeleton is a highly dynamic tissue whose structure relies on the balance between bone deposition and resorption. This equilibrium, which depends on osteoblast and osteoclast functions, is controlled by multiple factors that can be modulated post-translationally. Some of the modulators are Mitogen-activated kinases (MAPKs), whose role has been studied in vivo and in vitro. p38-MAPK modifies the transactivation ability of some key transcription factors in chondrocytes, osteoblasts and osteoclasts, which affects their differentiation and function. Several commercially available inhibitors have helped to determine p38 action on these processes. Although it is frequently mentioned in the literature, this chemical approach is not always as accurate as it should be. Conditional knockouts are a useful genetic tool that could unravel the role of p38 in shaping the skeleton. In this review, we will summarize the state of the art on p38 activity during osteoblast differentiation and function, and emphasize the triggers of this MAPK.

Background: miRNAs exert important roles during osteoblast proliferation and differentiation. Results: miR-322 induces expression of osteogenic genes by down-regulation of expression of Tob2, which binds to the 3Ј-UTR of Osx and modulates its degradation. Conclusion: miR-322 and its target Tob2 are regulators of osteogenesis through control of Osx mRNA degradation. Significance: We have identified a miRNA-transcription factor network that allows fine-tuning of the osteoblast differentiation program.

Bone morphogenetic proteins (BMPs) make up a family of morphogens that are critical for patterning, development, and function of the central and peripheral nervous system. Their effects on neural cells are pleiotropic and highly dynamic depending on the stage of development and the local niche. Neural cells display a broad expression profile of BMP ligands, receptors, and transducer molecules. Moreover, interactions of BMP signaling with other incoming morphogens and signaling pathways are crucial for most of these processes. The key role of BMP signaling suggests that it includes many regulatory mechanisms that restrict BMP activity both temporally and spatially. BMPs affect neural cell fate specification in a dynamic fashion. Initially they inhibit proliferation of neural precursors and promote the first steps in neuronal differentiation. Later on, BMP signaling effects switch from neuronal induction to promotion of astroglial identity and inhibition of neuronal or oligodendroglial lineage commitment. Furthermore, in postmitotic cells, BMPs regulate cell survival and death, to modulate neuronal subtype specification, promote dendritic and axonal growth and induce synapse formation and stabilization. In this review, we examine the canonical and non-canonical mechanisms of BMP signal transduction. Moreover, we focus on the specific role of BMPs in the nervous system including their ability to regulate neural stem cell proliferation, self-renewal, lineage specification, and neuronal function.