Mechanical Stretch Induced Osteogenesis on Human Annulus Fibrosus Cells through Upregulation of BMP-2/6 Heterodimer and Activation of P38 and SMAD1/5/8 Signaling Pathways.
Cheng-Nan ChenHsin-I ChangChia-Kung YenWen-Lung LiuKuo-Yuan HuangPublished in: Cells (2022)
Degenerative disc disease (DDD) is an important cause of low back pain. Repetitive tensile stress from the daily motion of the spine predisposes it to injury of the annulus fibrosus (AF) which causes IVD degeneration. This study aims to determine the causal relationship between mechanical stretch and osteogenesis in the AF cells of IVD as affected by bone morphogenic proteins (BMPs), specifically BMP-2/6 heterodimers. Our results found that 15% tensile stress (high cyclic stretching, HCS) may induce the expression of osteogenesis-related markers (Runx2, osterix) by upregulating BMP-2/6 heterodimeric ligands and their receptors on the human AF cell line. HCS also induced transient phosphorylation of p38 mitogen-activated protein (MAP) kinase and SMAD1/5/8. Neutralizing antibodies to the BMP-2/6 receptor (ALK3) blocked the expression of Runx2 and osterix, as well as the phosphorylation of p38 and SMAD1/5/8. In addition, treatment with a p38 MAPK inhibitor (SB203580) or siRNA to neutralize the effects of SMAD1/5/8 suppressed tensile stress-induced Runx2 and osterix expression. Mechanical stretching induces activation of p38 MAP kinase and SMAD1/5/8 signaling pathways, followed by the upregulation of BMP-2/6 heterodimer expression, thereby stimulating osteogenic Runx2 and osterix expression on AF cells. HCS may accelerate the progression of IVD degeneration by promoting an osteogenic response.
Keyphrases
- poor prognosis
- mesenchymal stem cells
- induced apoptosis
- bone regeneration
- epithelial mesenchymal transition
- stress induced
- signaling pathway
- atrial fibrillation
- transforming growth factor
- cell cycle arrest
- transcription factor
- long non coding rna
- endothelial cells
- binding protein
- bone marrow
- oxidative stress
- aortic valve
- cell proliferation
- pi k akt
- mass spectrometry
- zika virus
- physical activity
- cell death
- cancer therapy
- tyrosine kinase
- drug delivery
- high resolution
- smoking cessation
- pluripotent stem cells