P38 MAPK Signaling in Osteoblast Differentiation.

Eddie Rodríguez-Carballo,Beatriz Gámez,Francesc Ventura

doi:10.3389/fcell.2016.00040

Abstract

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.

Highlights

Two decades ago, the Mitogen-activated kinases (MAPKs) were revealed as key players in skeletal development and bone homeostasis that affect osteoblast commitment and differentiation
The purpose of this review is to describe the precise role of p38-MAPK on osteoblast differentiation and the several upstream events that can trigger its activation, in the interests of guiding anabolic therapies for bone-related pathologies
Bone tissue is composed of different cells and an extracellular matrix (ECM). This matrix has two components: one organic and another inorganic. The latter p38 MAPK Signaling in Osteoblast Differentiation is mainly formed by hydroxyapatite, which represents 99% of the body’s calcium and 80% of the body’s phosphate

Summary

Introduction

The Mitogen-activated kinases (MAPKs) were revealed as key players in skeletal development and bone homeostasis that affect osteoblast commitment and differentiation. There are hundreds of reports of in vivo and in vitro studies that analyse the relevant role of p38 and ERK throughout the osteoblastic commitment process, from a mesenchymal progenitor into a fully functional anabolic bone cell. This field of study has been facilitated by the availability of specific inhibitors of MAPK activity. MAPKs are a family of enzymes that are implicated in a series of processes in which extracellular stimuli (e.g., environmental stress, growth factors and cytokines) are transduced into different cellular actions.

Objectives

Findings

Conclusion