Related Experiment Video

Updated: Jan 12, 2026

Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
11:52

Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes

Published on: January 27, 2023

4.3K

MEK5 suppresses osteoblastic differentiation

Shoichi Kaneshiro1, Dai Otsuki2, Kiyoshi Yoshida2

  • 1Department of Orthopaedic Surgery, Japan Community Health Care Organization Osaka Hospital, 4-2-78 Fukushima, Fukushima Ward, Osaka City, Osaka 553-0003, Japan; Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Biochemical and Biophysical Research Communications
|May 23, 2015
PubMed

Insights

MAPK kinase 5 (MEK5) inhibits osteoblast differentiation but promotes cell proliferation. Inhibiting MEK5 signaling may offer a therapeutic strategy for osteoporosis treatment.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitogen-activated protein kinase (MAPK) signaling pathways regulate numerous cellular processes.
  • Extracellular signal-regulated kinase 5 (ERK5) is activated by MAPK kinase 5 (MEK5).
  • The role of MEK5 in osteoblastic differentiation remains largely unexplored.

Purpose of the Study:

  • To investigate the role of MEK5 in osteoblastic differentiation.
  • To explore MEK5's function in regulating osteoblast proliferation.

Main Methods:

  • Utilized MEK5 inhibitor BIX02189 in mouse preosteoblastic MC3T3-E1 and bone marrow stromal ST2 cells.
  • Employed small interfering RNA (siRNA) for MEK5 knockdown.
  • Performed gene expression analysis for osteoblastic markers (ALP, OCN, osterix).
  • Assessed extracellular matrix calcification and cell proliferation.

Main Results:

  • MEK5 inhibition (BIX02189 or siRNA) increased alkaline phosphatase (ALP) activity, osteocalcin (OCN), and osterix gene expression, enhancing matrix calcification.
  • MEK5 inhibition decreased osteoblastic cell proliferation at concentrations >0.5 μM.
  • MEK5 overexpression attenuated osteoblastic differentiation markers but promoted cell proliferation.

Conclusions:

  • MEK5 acts as a suppressor of osteoblastic differentiation.
  • MEK5 promotes osteoblastic cell proliferation.
  • Targeting MEK5 signaling presents a potential therapeutic avenue for osteoporosis.
Keywords:
MEK5MEK5 inhibitionMEK5 inhibitorOsteoblastic differentiation

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

7.1K
Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro07:51

Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro

Published on: March 18, 2019

6.3K

Related Concept Videos

Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
40.2K
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.9K
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
5.5K
Hormones and Bone Tissue01:17

Hormones and Bone Tissue

The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
3.6K
Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
8.3K
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...
10.4K