TNFα contributes for attenuating both Y397FAK and Y416Src phosphorylations in osteoblasts

Adm Cavagis1, Er Takamori, Jm Granjeiro

  • 1Federal University of São Carlos (UFSCar), Sorocaba, Brazil.

Oral Diseases
|October 30, 2013
PubMed
Abstract

Insights

Tumor necrosis factor-alpha (TNFα) reduces osteoblast function by decreasing focal adhesion kinase (FAK) and Src activity. This inflammatory mediator impacts osteoblast adhesion and performance, revealing a novel regulatory role.

Area of Science:

  • Cell Biology
  • Immunology
  • Biochemistry

Background:

  • Inflammatory mediators significantly impact bone cell function.
  • Osteoblast behavior is poorly understood in the context of inflammation.

Purpose of the Study:

  • Investigate the effect of tumor necrosis factor-alpha (TNFα) on focal adhesion kinase (FAK) and Src phosphorylation in osteoblasts.
  • Elucidate the role of inflammatory mediators in regulating osteoblast activity.

Main Methods:

  • MC3T3-E1 pre-osteoblast cells were treated with TNFα or macrophage-conditioned medium.
  • Immunoblotting was used to assess FAK and Src phosphorylation.
  • ELISA measured TNFα levels, and neutralizing antibodies were employed.

Main Results:

  • TNFα treatment significantly attenuated FAK (Y397) and Src (Y416) phosphorylation, indicating reduced activity.
  • Conditioned medium from LPS-stimulated macrophages mimicked this effect.
  • Anti-TNFα antibodies diminished the effects of conditioned medium, confirming TNFα's role.
  • TNFα was shown to impair osteoblast adhesion.

Conclusions:

  • Mediators from LPS-stimulated macrophages, particularly TNFα, attenuate FAK and Src activation in osteoblasts.
  • TNFα plays a novel role in regulating osteoblast performance and adhesion.

Related Concept Videos

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...
7.7K
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...
7.2K
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
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
64.7K
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.0K
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...
3.5K