Mechanical stress affects the osteogenic differentiation of human ligamentum flavum cells via the BMP‑Smad1 signaling pathway

Mol Med Rep. 2017 Nov;16(5):7692-7698. doi: 10.3892/mmr.2017.7543. Epub 2017 Sep 20.

Abstract

The aim of the present study was to investigate the effects of mechanical stress on the osteogenic differentiation of human ligamentum flavum cells via the bone morphogenetic protein (BMP)‑Smad1 signaling pathway. Mechanical stress increased cell proliferation and induced osteogenic differentiation of human cells derived from the ossification of the ligamentum flavum (OLF). In addition, mechanical stress activated osteocalcin (OC), alkaline phosphatase (ALP) and runt‑related transcription factor 2 (RUNX‑2) mRNA expression, and suppressed Ets proto‑oncogene 1 (Ets‑1) and sex determining region Y‑box 2 (SOX‑2) mRNA expression in OLF cells. Src protein expression was suppressed by mechanical stress in human OLF cells. In addition, the protein expression levels of BMP, phosphorylated (p)‑mothers against decapentaplegic homolog‑1 (Smad1) and p‑p38‑mitogen‑activated protein kinases (p38MAPK) were increased by mechanical stress. These results demonstrate that mechanical stress effectively increases cell proliferation, promotes the osteogenic differentiation rate of OLF cells, activates OC, ALP and RUNX‑2, and suppresses Ets‑1 and SOX‑2 potentially via the BMP‑Smad1 and Src‑p38MAPK signaling pathways.

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Biomechanical Phenomena
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Differentiation
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Gene Expression Regulation
  • Humans
  • Ligamentum Flavum / metabolism*
  • Ligamentum Flavum / pathology
  • Male
  • Mechanotransduction, Cellular*
  • Middle Aged
  • Osteoblasts / metabolism*
  • Osteoblasts / pathology
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis / genetics*
  • Primary Cell Culture
  • Proto-Oncogene Protein c-ets-1 / genetics
  • Proto-Oncogene Protein c-ets-1 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Smad1 Protein / genetics
  • Smad1 Protein / metabolism*
  • Stress, Mechanical
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism

Substances

  • Bone Morphogenetic Proteins
  • Core Binding Factor Alpha 1 Subunit
  • ETS1 protein, human
  • Proto-Oncogene Protein c-ets-1
  • RNA, Messenger
  • Runx2 protein, mouse
  • SMAD1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Smad1 Protein
  • Osteocalcin
  • src-Family Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Alkaline Phosphatase