Osteoclastogenesis is Repressed by Mechanical Strain in an In Vitro Model

Rubin, Jeffrey S.; Fan, Xian; Biskobing, Diane M.; Taylor, W. Robert; Rubin, Clinton T.

doi:10.2106/00004623-200003000-00031

Cited by 21 publications

(38 citation statements)

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“…Given that calcium oscillation could enhance the resorption ability of osteoclasts, 15 high FSS level might inhibit the functions of osteoclasts. Some studies showed that high mechanical stretching strain can inhibit the formation of osteoclasts, 8,14 but a cell-level experiment demonstrated that TRAP activity and the number and size of resorption pits increased with increasing FSS (6-20 dyne/cm 2 ) on osteoclasts. 11 Therefore, it is necessary to clarify the correlation among FSS levels, calcium response of osteoclasts, and bone resorption in the future.…”

Section: Discussionmentioning

confidence: 99%

Fluid Flow-Induced Calcium Response in Early or Late Differentiated Osteoclasts

Sun

et al. 2012

Ann Biomed Eng

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Abstract-Intracellular calcium oscillation caused by receptor activator of nuclear factor kappa-B ligand has been demonstrated to promote the differentiation of osteoclasts. Osteoclasts are recruited on the surface of trabeculae, and are exposed to fluid flow caused by the deformation of the bone matrix. However, the roles of fluid shear stress (FSS) on calcium response during the differentiation process of osteoclasts are still unknown. In the current study, the formation of tartrate-resistant acid phosphatase-positive, multinucleated osteoclasts from RAW264.7 macrophage cells were induced by co-culturing them with the conditioned medium from MC3T3-E1 osteoblasts. The in situ observations showed a high correlation between the area and the nuclear number of osteoclasts. The cells were stimulated by FSS at different levels (1 or 10 dyne/cm 2 ) before (0 day) or after being induced for 4 or 8 days. The mechanically-induced calcium response was recorded and analyzed. The results indicated a different property of calcium oscillation for the osteoclasts in different fusion stages (i.e., more calciumresponsive peaks appeared in small osteoclasts than those in the larger ones). The rates of calcium influx decreased and the time of recovery in osteoclast cytosol increased along with the fusion of osteoclasts. In addition, increasing the FSS level enhanced the calcium oscillation of osteoclasts at early induction (4 days). However, this effect was weakened at the late induction (8 days). The present work could help provide understanding regarding the mechanism of the involvement of calcium in mechanically induced bone remodeling.

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Section: Discussionmentioning

confidence: 99%

Fluid Flow-Induced Calcium Response in Early or Late Differentiated Osteoclasts

Sun

et al. 2012

Ann Biomed Eng

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“…Li et al found that marrow stromal cells change their proliferation rate and gene expression patterns in response to mechanical stimulation (Li et al, 2004). With respect to osteoclast number: stromal cell expression of the osteoclastogenic facto, RANKL is sensitive to mechanical force (Rubin et al, 1999(Rubin et al, , 2002c, suggesting that the number of osteoclasts present is controlled through mechanical regulation sensed by stromal cells. However, the osteoclast itself has also been shown to respond to mechanical signals adding another layer of control by which mechanical force might limit bone resorption (Wiltink et al, 1995).…”

Section: Mechanosensitive Bone Cellsmentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

400

303

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Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

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“…Osteoclastogenesis has been shown to be regulated by mechanical loading both in vitro and in vivo (17,19,21,(40)(41)(42)(43). Rubin and colleagues (40)(41)(42)(43) have shown that dynamic mechanical strain can decrease osteoclast formation by about 50% in primary marrow cultures, and this is mediated through a decrease in RANKL and an increase in eNOS-generated NO in bone marrow stromal cells.…”

Section: Introductionmentioning

confidence: 99%

“…Rubin and colleagues (40)(41)(42)(43) have shown that dynamic mechanical strain can decrease osteoclast formation by about 50% in primary marrow cultures, and this is mediated through a decrease in RANKL and an increase in eNOS-generated NO in bone marrow stromal cells. OPG expression at both the gene and the protein level has also been shown to be regulated by mechanical stimulation (21,45).…”

Section: Introductionmentioning

confidence: 99%

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

You

Temiyasathit

Lee

et al. 2008

Bone

289

156

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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 in vitro studies have shown that osteocytes support osteoclast formation and activation when co-cultured with osteoclast precursors. In this study, we examined the osteocytes' role in the mechanical regulation of osteoclast formation and activation.We demonstrated here that 1) Mechanical stimulation of MLO-Y4 osteocyte-like cells decreases their osteoclastogenic-support potential when co-cultured with RAW264.7 monocyte osteoclast precursors, 2) Soluble factors released by these mechanically stimulated MLO-Y4 cells inhibit osteoclastogenesis induced by ST2 bone marrow stromal cells or MLO-Y4 cells, and 3) Soluble RANKL and OPG were released by MLO-Y4 cells, and the expressions of both were found to be mechanically regulated.Our data suggests that mechanical loading decreases the osteocyte's potential to induce osteoclast formation by direct cell-cell contact. However, it is not clear that osteocytes in vivo are able to form contacts with osteoclast precursors. Our data also demonstrates that mechanically stimulated osteocytes release soluble factors that can inhibit osteoclastogenesis induced by other supporting

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Osteoclastogenesis is Repressed by Mechanical Strain in an In Vitro Model

Cited by 21 publications

References 0 publications

Fluid Flow-Induced Calcium Response in Early or Late Differentiated Osteoclasts

Fluid Flow-Induced Calcium Response in Early or Late Differentiated Osteoclasts

Molecular pathways mediating mechanical signaling in bone

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

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