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Int J Clin Exp Pathol 2013;6(5):841-852
Overexpression of integrin a2 promotes osteogenic differentiation of hBMSCs from
senile osteoporosis through the ERK pathway
Hui-Min Hu, Liu Yang, Zhe Wang, Yan-Wu Liu, Jin-Zhu Fan, Jing Fan, Jian Liu, Zhuo-Jing Luo
Department of Orthopaedics, Xi-jing Hospital, Fourth Military Medical University, No. 15, Changle West Road, Xi’an, Shaanxi Province, 710032,
P. R. China. Equal contributors.
Received February 19, 2013; Accepted March 16, 2013; Epub April 15, 2013; Published May 1, 2013
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. Conclusion: 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. (IJCEP1302026).
Keywords: Osteoporosis, human bone marrow stromal cells, integrin, ERK pathway
Address correspondence to: Dr. Zhuo-Jing Luo, Department of Orthopaedics, Xi-jing Hospital, Fourth Military Medical University, No. 15,
Changle West Road, Xi’an, Shaanxi Province, 710032, P. R. China. E-mail: email@example.com; Dr. Jian Liu, Department of Orthopaedics, Xi-
jing Hospital, Fourth Military Medical University, No. 15, Changle West Road, Xi’an, Shaanxi Province, 710032, P. R. China. E-mail: