To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell’s actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.
Susan A. Bloomfield
William M. Sherman, Julie M. Lash, John C. Simonsen and Susan A. Bloomfield
Because muscle damage from eccentric exercise has been associated with alterations in muscle glycogen metabolism, this study determined the effects of exercise on the insulin and glucose responses to an oral glucose tolerance test (OGTT). In a repeated-measures design, 11 subjects undertook either no exercise, 2 min of isokinetic leg exercise, or 50 min of level or downhill running. No exercise was performed and diet was controlled during the 48 hrs after the treatments and before the OGTT. Ratings of muscle soreness and CK activity were significantly elevated 48 hrs after downhill running. Level running also increased CK activity but did not induce muscle soreness. Isokinetic exercise did not affect either one. Blood glucose responses to the OGTT were similar among the treatments. In contrast, the insulin responses to the OGTT following downhill running were significantly increased. These results suggest that eccentric exercise associated with downhill running that results in delayed muscle soreness is associated with the development of a mild insulin-resistant condition.