Related Experiment Video

Updated: Mar 29, 2026

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

5.2K

Tmem178 acts in a novel negative feedback loop targeting NFATc1 to regulate bone mass

Corinne E Decker1, Zhengfeng Yang2, Ryan Rimer3

  • 1Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University School of Medicine, St. Louis, MO 63110; Graduate Program in Immunology, Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO 63110;

Proceedings of the National Academy of Sciences of the United States of America
|December 9, 2015
PubMed

Insights

Transmembrane protein 178 (Tmem178) regulates calcium signaling essential for osteoclast formation. Loss of Tmem178 enhances bone loss, highlighting its role in maintaining skeletal mass and preventing pathological conditions.

Area of Science:

  • Skeletal Biology
  • Immunology
  • Cell Signaling

Background:

  • Phospholipase C gamma-2 (PLCγ2) signaling and calcium (Ca2+) oscillations are crucial for nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) activation, driving osteoclastogenesis.
  • Osteoclastogenesis is vital for skeletal remodeling but also implicated in pathological bone loss.

Purpose of the Study:

  • To identify the function of transmembrane protein 178 (Tmem178), a PLCγ2 downstream target, in regulating the NFATc1 axis.
  • To investigate the role of Tmem178 in skeletal homeostasis and pathological bone loss.

Main Methods:

  • Utilized knockout mouse models (Tmem178(-/-) and PLCγ2(-/-)) to assess skeletal phenotypes.
  • Investigated Tmem178 localization and function in regulating calcium fluxes at the ER membrane.
  • Analyzed human CD14(+) monocytes from patients with systemic juvenile idiopathic arthritis.

Main Results:

  • Tmem178(-/-) mice exhibit osteopenia and increased susceptibility to inflammatory bone loss due to enhanced osteoclast formation, contrasting with PLCγ2(-/-) mice.
  • Tmem178 localizes to the ER membrane and modulates RANKL-induced Ca2+ fluxes, thereby controlling NFATc1 induction.
  • Down-regulation of Tmem178 in human monocytes correlates with excessive osteoclastogenesis, particularly in patients with systemic juvenile idiopathic arthritis.

Conclusions:

  • Tmem178 acts as a critical modulator of the NFATc1 axis, essential for maintaining skeletal mass.
  • Tmem178 plays a key role in limiting pathological bone loss by controlling osteoclast formation.
  • Dysregulation of Tmem178 is linked to excessive osteoclastogenesis and bone loss in inflammatory conditions.
Keywords:
NFATc1Tmem178calciumosteoclastssJIA

More Related Videos

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia09:52

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia

Published on: December 4, 2018

8.2K
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

6.4K

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...
10.9K
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...
4.2K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.3K
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.
41.0K
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...
4.7K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
8.0K