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A model is presented that provides a resolution to a fundamental paradox in bone physiology, namely, that the strains applied to whole bone (i.e., tissue level strains) are much smaller (0.04-0.3 percent) than the strains (1-10 percent) that are necessary to cause bone signaling in deformed cell cultures (Rubin and Lanyon, J. Bone Joint Surg. 66A (1984)(More)
Fatigue loading causes a spatial distribution of osteocyte apoptosis co-localized with bone resorption spaces peaking around microdamage sites. Since osteocytes have been shown to regulate osteoclast formation and activity, we hypothesize that osteocyte apoptosis regulates osteoclastogenesis. In this study, we used serum-starvation to mimic reduced nutrient(More)
Bone tissue forms and is remodeled in response to the mechanical forces that it experiences, a phenomenon described by Wolff's Law. Mechanically induced formation and adaptation of bone tissue is mediated by bone cells that sense and respond to local mechanical cues. In this review, the forces experienced by bone cells, the mechanotransduction pathways(More)
Bone has the ability to adjust its structure to meet its mechanical environment. The prevailing view of bone mechanobiology is that osteocytes are responsible for detecting and responding to mechanical loading and initiating the bone adaptation process. However, how osteocytes signal effector cells and initiate bone turnover is not well understood. Recent(More)
Mechanical loading is an important regulator of bone formation and bone loss. Decreased osteoblast number and function are important cellular mechanisms by which mechanical disuse leads to decreased bone formation. Decreased osteoblast number may be a result of decreased osteoprogenitor proliferation, differentiation, or both. However, the effects of(More)
Structural adaptation of the bone tissue is mediated by loading-induced interstitial fluid flow within the bone microstructure. Within this framework, osteocytes fulfill the central mechanotransductive role in the bone remodeling process. While osteocytes have been demonstrated to be exquisitely sensitive to various forms of fluid flow stimulus in vitro,(More)
Fluid flow due to loading in bone is a potent mechanical signal that may play an important role in bone adaptation to its mechanical environment. Previous in vitro studies of osteoblastic cells revealed that the upregulation of cyclooxygenase-2 (COX-2) and c-fos induced by steady fluid flow depends on a change in actin polymerization dynamics and the(More)
Physical activity creates deformation in bone that leads to localized pressure gradients that drive interstitial fluid flow. Due to the cyclic nature of the applied load, this flow is oscillatory by nature. Oscillatory fluid flow (OFF) may lead to positive bone remodeling through effects on both osteoblasts and osteoclasts but its effect on(More)
Osteocyte apoptosis precedes osteoclast resorption, and may act as a critical signal to trigger bone remodeling. While osteoclast precursors are known to travel via the circulation, the specific mechanisms by which they accumulate at remodeling sites are unclear. We hypothesized that osteocyte apoptosis mediates osteoclast precursor adhesion to vascular(More)
Osteocyte apoptosis, associated with reduced interstitial fluid flow, precedes osteoclast precursor recruitment and may aid in the delivery of osteoclast precursors to the remodeling site by promoting angiogenesis. To test the association between fluid flow and osteocyte apoptosis, osteocyte-like MLO-Y4 cells were subjected to either oscillatory fluid flow(More)