title: Overexpression of integrin a2 promotes osteogenic differentiation of hBMSCs from senile osteoporosis through the ERK pathway.
abstract: Osteoporosis is a major health problem affecting the aging population, especially in patients 65 years of age and older. The imbalance between bone formation and bone resorption is generally accepted as the essential mechanism leading to osteoporosis. In addition to the abnormal activation of osteoclast-mediated bone resorption, the dysfunction of bone marrow stromal cells (BMSCs) in mediating bone formation has been accepted as a major contributor to the progression of senile osteoporosis.
  
  
  RESULTS
  In our study, senile osteoporotic hBMSCs displayed a decreasing capacity for proliferation and osteoblast differentiation, which was associated with the downregulation of integrin α2. Forced ectopic integrin α2 expression using a lentivirus vector reversed the dysfunction of senile osteoporotic hBMSCs. Additionally, the overexpression of integrin α2 upregulated the levels of Runx2 and Osterix. Mechanically, Western blot analyses revealed that integrin α2 phosphorylated ERK1/2 and the inactivation of ERK by PD98059 suppressed the osteoblastic differentiation of hBMSCs, suggesting that integrin α2 promotes osteoblast proliferation through the activation of ERK1/2 MAPK.
  
  
  CONCLUSIONS
  Taken together, our results show that hBMSCs obtained from senile osteoporotic patients gradually lose their capability to differentiate along the osteogenic lineage and proliferate, which might be associated with the abnormal regulation of the integrin α2/ERK/Runx2 signaling pathway undergoing senile osteoporosis.
authors: Department of Orthopaedics, Xi-jing Hospital, Fourth Military Medical University, No. 15, Changle West Road, Xi'an, Shaanxi Province, 710032, P. R. China.
authors: Hui-Min
authors: HM
authors: Hu
authors: Liu
authors: L
authors: Yang
authors: Zhe
authors: Z
authors: Wang
authors: Yan-Wu
authors: YW
authors: Liu
authors: Jin-Zhu
authors: JZ
authors: Fan
authors: Jing
authors: J
authors: Fan
authors: Jian
authors: J
authors: Liu
authors: Zhuo-Jing
authors: ZJ
authors: Luo
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D039421:Integrin alpha2 / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology; D010024:Osteoporosis / Q000378:metabolism* / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D039421:Integrin alpha2
keywords: ERK pathway; Osteoporosis; human bone marrow stromal cells; integrin
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