Influence of Mechanical Forces on Bone-Forming Cells

6 Influence of Mechanical Forces on Bone-Forming Cells 

Osteocytes are formed by the incorporation of osteoblasts into bone matrix. They remain in contact with other osteocytes via gap junction-coupled cell processes that form small channels through the matrix, the canaliculi. These small channels connect the cell body containing lacunae with each other and ECM external to the bone and play an important role in mechano-chemical transduction. 

Parathyroid hormone (PTH) is an 84-amino acid polypeptide hormone that mediates bone remodeling and is an essential regulator of calcium homeostasis. Prolonged exposure to PTH changes the phenotype of the osteoblast from a cell involved in bone formation to one directing bone 

Osteoblasts subjected to fluid shear increase expression of the early response gene, c-fos, and the inducible isoform of cyclooxygenase, COX-2, two proteins linked to anabolic response of bone to mechanical stimulation. Flow-induced responses in osteoblasts are mediated by inositol triphosphate intracellular calcium release. Flow-mediated stress is reported to induce both PGE2 and NO production. Fluid shear stress stimulates NO release by two distinct pathways a G-protein and calcium-dependent phase sensitive to flow gradients, and a G-protein and calcium-independent pathway stimulated by sustained flow. 

The application of tensile stresses to osteoblasts appears to cause induction of the BMP-4 gene in preosteoblastic cells and adjacent spindle-shaped fibroblasts suggesting that BMP-4 may play a pivotal role by acting as an autocrine and a paracrine factor for recruiting osteoblasts in tensile stress-induced osteogenesis. Intermittent hydrostatic pressure (IHC) up-regulates osteopontin (OPN) mRNA expression in osteoblast cell cultures. In both 

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