Related Experiment Video

Updated: May 10, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

Mitogen-activated protein kinase pathways in osteoblasts

Matthew B Greenblatt1, Jae-Hyuck Shim, Laurie H Glimcher

  • 1Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115;

Annual Review of Cell and Developmental Biology
|June 4, 2013
PubMed

Insights

Mitogen-activated protein kinase (MAPK) pathways regulate bone mass by controlling osteoblast differentiation. Key MAPKs like ERK and p38 directly influence RUNX2, the master regulator of bone formation.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Skeletal Biology

Background:

  • Mitogen-activated protein kinases (MAPKs) are crucial signaling molecules involved in inflammation and cancer.
  • Recent research highlights their role in developmental processes, including bone mass regulation through osteoblast differentiation.

Purpose of the Study:

  • To review the functions of MAPK pathways in osteoblasts.
  • To elucidate the specific roles of MAPK substrates in osteoblast differentiation and function.

Main Methods:

  • Review of existing literature on MAPK signaling in osteoblasts.
  • Analysis of MAPK substrates, including RUNX2, RSK2, and ATF4.
  • Comparison of MAPK pathway wiring in osteoblasts versus other cell types.

Main Results:

  • MAPK pathways, particularly ERK and p38, directly phosphorylate RUNX2, a master regulator of osteoblast differentiation.
  • ERK activation of RSK2 leads to ATF4 phosphorylation, impacting late-stage osteoblast functions.
  • Distinct differences exist in MAPK pathway organization within osteoblasts compared to other tissues.

Conclusions:

  • MAPK signaling is critical for maintaining bone mass by regulating key osteoblast differentiation factors.
  • Understanding these pathways provides insights into skeletal biology and potential therapeutic targets.
  • The specific mechanisms of MAPK action in osteoblasts reveal complex in vivo signaling networks.

More Related Videos

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro07:03

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro

Published on: June 16, 2022

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...