Related Experiment Video
Updated: Jul 16, 2026

Simple Establishment of a Vascularized Osteogenic Bone Marrow Niche Using Pre-Cast Poly(ethylene Glycol) (PEG) Hydrogels in an Imaging Microplate
Published on: May 19, 2023
TNF-alpha inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling
Tomoyuki Mukai1, Fumio Otsuka, Hiroyuki Otani
1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama City 700-8558, Japan.
Abstract:
The cellular mechanism by which TNF-alpha inhibits osteoblastic differentiation induced by BMPs was investigated using mouse myoblast C2C12 cells expressing functional BMP receptors and Smad signaling molecules except ALK-6. Osteoblast transformation in response to BMP-2 was morphologically suppressed by TNF-alpha. Expression of biological markers for osteoblasts including Runx2 and osteocalcin, alkaline phosphatase activity, and parathyroid hormone (PTH) responsiveness shown by PTH-induced cAMP production were readily activated by BMP-2, -4, -6, and -7. The BMP-induced osteoblastic phenotype was dose-dependently inhibited by TNF-alpha. BMP-induced Smad1,5,8 phosphorylation of C2C12 cells was suppressed by TNF-alpha signaling. In addition, cDNA array analysis showed an increased expression of inhibitory Smad6 by TNF-alpha. MAP kinase analysis showed that ERK1/ERK2 and SAPK/JNK phosphorylation were selectively activated by TNF-alpha regardless of the presence of BMP ligands. BMPs had no effect on expression levels of TNF type 1 and 2 receptors. Notably, inhibition of SAPK/JNK restored TNF-alpha effects on BMP-induced osteoblast differentiation demonstrated by Id-1-promoter activity as well as Runx2 and osteocalcin mRNA levels. Collectively, TNF-alpha elicits BMP-induced osteogenic inhibition by suppressing BMP-Smad signaling pathway, at least in part, through SAPK/JNK activation and Smad6 upregulation.
Related Concept Videos
TGF - β Signaling Pathway
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
The JAK-STAT Signaling Pathway
NF-kB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
MAPK Signaling Cascades
Enzyme-linked Receptors
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...
