Hypergravity stimulates collagen synthesis in human osteoblast-like cells:Evidence for the involvement of p44/42 MAP-kinases (ERK 1/2)

The formation and organization of skeletal tissue is strongly influenced by mechanical stimulation. There is increasing evidence that gravitational st ress has an impact on the expression of early response genes in mammalian c ells and may play a role in the formation of extracellular matrix, In parti cular, osteoblasts may be unique in their response to gravitational stimuli since in these cells microgravity has been reported to reduce collagen syn thesis, while in fibroblasts the opposite effect was observed. Here, we har e investigated the influence of hypergravity induced by centrifugation on t he collagen synthesis of human osteoblast-like cells (hOB) and studied the possible involvement of the mitogen-activated protein (MAP) kinase signalin g cascade. Collagen synthesis was significantly increased by 42 +/- 16% und er hypergravity at 13 x g, an effect paralleled by the enhanced expression of the collagen I alpha 2 (COL1A2) mRNA, No difference was seen in the prop ortion of collagen types I, III, and V synthesized by hOB, Hypergravity ind uced a markedly elevated phosphorylation of the p44/42 MAP kinases (ERK 1/2 ). The inhibition of this pathway suppressed the hypergravity-induced stimu lation of both collagen synthesis as well as COL1A2 mRNA expression by abou t 50%. Our results show that the collagen synthesis of non-transformed hOB is stimulated under hypergravitational conditions. This response appears to be partially mediated by the MAP kinase pathway.