Sensitivity of osteocytes to biomechanical stress in vitro

Klein‐Nulend, Jenneke; Plas, A. van der; Semeins, Cornelis M.; Ajubi, N.E.; Frangos, John A.; Nijweide, Peter J.; Burgér, E.H.

doi:10.1096/fasebj.9.5.7896017

Cited by 707 publications

(514 citation statements)

References 11 publications

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“…eNOS global knockout animals exhibit lower BMD, bone formation, and osteoblast activity; with little to no effect on bone resorption, suggesting NO may be important for osteoblast function 49, 50. Previous research shows NO synthesis is induced in osteoblasts and osteocytes by mechanical strain and shear stress 51, 52, 53, 54.…”

Section: Discussionmentioning

confidence: 99%

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

Conley

Roberts

Sharpton

et al. 2017

Molecular Nutrition Food Res

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ScopeStudies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age‐related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss.Methods and resultsSix‐month‐old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham‐operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low‐dose nitrate (LDN, 0.1 mmol nitrate/kg bw/day), or (iii) high‐dose nitrate (HDN, 1.0 mmol nitrate/kg bw/day) for three weeks. The sham received vehicle. Serum bone turnover markers; bone mass, mineral density, and quality; histomorphometric parameters; and fecal microbiome were examined. Three weeks of LDN or HDN improved NO bioavailability in a dose‐dependent manner. OVX resulted in cancellous bone loss, increased bone turnover, and fecal microbiome changes. OVX increased relative abundances of Firmicutes and decreased Bacteroideceae and Alcaligenaceae. Nitrate did not affect the skeleton or fecal microbiome.ConclusionThese data indicate that OVX affects the fecal microbiome and that the gut microbiome is associated with bone mass. Three weeks of nitrate supplementation does not slow bone loss or alter the fecal microbiome in OVX.

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Section: Discussionmentioning

confidence: 99%

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

Conley

Roberts

Sharpton

et al. 2017

Molecular Nutrition Food Res

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“…Osteocytes are the most abundant cell type in bone. Their location, embedded in the mineralized bone tissue, and demonstrated mechanosensitivity suggest they function as cellular mechanotransducers (5,23). Furthermore, recent studies have shown that osteocytes can support osteoclast formation and activation by direct cell-cell contact with osteoclast precursors (10,60).…”

Section: Discussionmentioning

confidence: 99%

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

You

Temiyasathit

Lee

et al. 2008

Bone

291

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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“…In other words, the microarchitecture of the bone tissue could serve to indirectly (fluid pressure through cannaliculi) or directly (strain amplification via the lacunae) amplify the strain signal. While some have suggested that osteocytes might be more sensitive to shear than, for instance, transient pressure (Klein-Nulend et al, 1995), there are divergent opinions: e.g., substrate strain prevents osteocyte apoptosis (Plotkin et al, 2005). Recently Han and coworkers have developed a 3D model for the osteocyte process and used large-deformation "elastica" theory to predict the deformed shape of the cell (Han et al, 2004).…”

Section: Mechanosensitive Bone Cellsmentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

402

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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Sensitivity of osteocytes to biomechanical stress in vitro

Cited by 707 publications

References 11 publications

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

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

Molecular pathways mediating mechanical signaling in bone

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