Fs. Wang et al., Physical shock wave mediates membrane hyperpolarization and ras activationfor osteogenesis in human bone marrow stromal cells, BIOC BIOP R, 287(3), 2001, pp. 648-655
Citations number
33
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Physical shock wave (SW) has shown effectiveness on promotion of bone growt
h. We have recently demonstrated that SW could promote bone marrow stromal
cell differentiation toward osteoprogenitor associated with induction of TG
F-beta1. We have further demonstrated that SW-induced membrane hyperpolariz
ation and Ras activation acted an early signal for the osteogenesis in huma
n bone marrow stromal cells. An optimal dose of SW treatment at 0.16 mj/mm(
2) for 500 impulses induced a rapid membrane hyperpolarization in 5 min, ac
tivation of Ras in 30 min, and cell proliferation in 2 days. The SW-promote
d cell growth was related to osteogenesis as demonstrated by increase of bo
ne alkaline phosphatase activity in 6 days and osteocalcin mRNA expression
in 12 days. In support that SW-induced Ras activation mediated osteogenesis
of human bone marrow stromal cells, we further demonstrated that transfect
ion of bone marrow stromal cells with a dominant negative Ras mutant (Asn-1
7 ras(H)) abrogated the SW enhancement of osteogenic transcription factor (
CBFA1) activation, osteocalcin mRNA expression, and bone nodule formations
These results suggest that physical SW promotes bone marrow stromal cell di
fferentiation toward osteogenic lineage via membrane hyperpolarization, fol
lowed by Ras activation and specific osteogenic transcription factor CBFA1
expression. A link between physical SW and biomembrane perturbation-mediate
d Ras activation may highlight how noninvasive physical agents could be use
d to promote fracture healing and to rescue patients with osteoporosis and
osteopenic disorders in the future. (C) 2001 Academic Press.