Related Experiment Video

Updated: Jun 20, 2026

Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
06:47

Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells

Published on: May 4, 2018

Vimentin inhibits ATF4-mediated osteocalcin transcription and osteoblast differentiation

Na Lian1, Weiguang Wang, Lingzhen Li

  • 1Department of Medicine, Vanderbilt University Center for Bone Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

The Journal of Biological Chemistry
|September 4, 2009
PubMed

Insights

Vimentin, a cytoskeletal protein, binds to Activating Transcription Factor 4 (ATF4) and inhibits osteoblast differentiation. Reducing vimentin levels promotes osteocalcin transcription in immature bone cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Activating transcription factor 4 (ATF4) is crucial for osteoblast differentiation and osteocalcin gene regulation.
  • Identifying ATF4's functional partners is key to understanding osteoblast biology.

Purpose of the Study:

  • To identify proteins interacting with ATF4 in osteoblasts.
  • To elucidate the functional role of identified partners in ATF4-mediated osteoblast differentiation.

Main Methods:

  • Affinity chromatography using recombinant His-ATF4 and osteoblast nuclear extracts.
  • Liquid chromatography-mass spectrometry for protein identification.
  • Coimmunoprecipitation, pulldown assays, DNA cotransfection, gel retardation, Northern hybridization, and small interfering RNA (siRNA) for functional validation.

Main Results:

  • Vimentin was identified as an ATF4-interacting protein, binding via ATF4's leucine zipper domain.
  • Vimentin inhibits ATF4's transactivation of osteocalcin by blocking ATF4 binding to the OSE1 site.
  • Vimentin expression is high in immature osteoblasts and low in mature osteoblasts.
  • Vimentin knockdown enhances osteocalcin transcription in immature osteoblasts.
  • Vimentin overexpression impairs osteoblast differentiation markers (alkaline phosphatase, mineralization, bone sialoprotein, osteocalcin).

Conclusions:

  • Vimentin acts as a negative regulator of osteoblast differentiation.
  • Vimentin interacts with ATF4 to suppress osteocalcin expression and inhibit terminal differentiation in immature osteoblasts.
  • This interaction represents a novel mechanism controlling osteoblast maturation.

More Related Videos

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

Related Concept Videos

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...
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 bone...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Bone Remodeling and Repair01:31

Bone Remodeling and Repair

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 bone...