Mechanical strain promotes osteoblastic differentiation through integrin-β1-mediated β-catenin signaling.
As integrins are mechanoresponsive, there exists an intimate relationship between integrins and mechanical strain. Integrin-β1 mediates the impact of mechanical strain on bone. Mechanical strain induces bone formation through the activation of β-catenin pathways, which suggests that integrin-β1 mediates β-catenin signaling in osteoblasts in response to mechanical strain. In the present study, we examined the role of integrin-β1 in Wnt/β-catenin signal transduction in mechanically strained osteoblasts. MC3T3-E1 osteoblastic cells were transfected with integrin-β1 small interfering RNA (si-Itgβ1), and exposed to mechanical tensile strain of 2,500 microstrain (µε) using a four-point bending device. The mechanical strain enhanced the mRNA expression of integrin-β1, the protein levels of phosphorylated (p-) glycogen synthase kinase-3β (GSK‑3β) and β-catenin, simultaneously increased the mRNA levels of runt-related transcriptional factor 2 (Runx2) and osteocalcin (OCN), the protein levels of bone morphogenetic protein (BMP)-2 and -4 and enhanced the alkaline phosphatase (ALP) activity of the ME3T3-E1 cells. The elevations were inhibited by si-Itgβ1. Additionally, the mechanical strain induced the nuclear translocation of β-catenin into the nucleus, which was also inhibited by si-Itgβ1. These findings indicated that mechanical strain promoted osteoblastic differentiation through integrin‑β1‑mediated β-catenin signaling.
College of Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, P.R. China.
Yuxian
Y
Yan
School of Physical Science and Technology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Haoyang
H
Sun
College of Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, P.R. China.
Yuanwei
Y
Gong
College of Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, P.R. China.
Zhixiong
Z
Yan
College of Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, P.R. China.
Xizheng
X
Zhang
College of Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, P.R. China.
Yong
Y
Guo
College of Biotechnology, Guilin Medical University, Guilin, Guangxi 541100, P.R. China.
Yang
Y
Wang
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D055785:Gene Knockdown Techniques; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D051176:beta Catenin / Q000378:metabolism*
D050659:Core Binding Factor Alpha 1 Subunit; D019012:Integrin beta1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D000469:Alkaline Phosphatase