A model for the role of integrins in flow induced mechanotransduction in osteyocytes

Wang, Hong; McNamara,; Schaffler,; Weinbaum,

doi:10.1109/nebc.2007.4413269

Cited by 11 publications

(15 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Osteocytes are the main mechanosensors in bone and are subjected to various forms of mechanical loading [14,69,70]. Therefore to capture the in vivo environment more accurately, all osteocytes were subjected to oscillatory uid ow.…”

Section: Mechanical Stimulationmentioning

confidence: 99%

“…Laminar oscillatory uid ow was applied to OCY454 cells using a parallel plate system, which comprised of a syringe pump (NE-1600, New Era Pump Systems, Farmingdale, NY, USA), parallel plate chambers and individual media reservoirs connected through gas-permeable silicone tubing (Cole-Parmer, Vernon Hills, IL, USA) [47]. The OFF loading regime subjected the OCY454 cells to a shear stress of 1 Pa at 0.5 Hz for 1 h, which is within the range of shear stresses experiences by osteocytes in vivo [69,[71][72][73]. Before and after oscillatory uid ow, slides were rinsed with PBS (x3) to remove residual media, to ensure that conditioned media collected did not contain 17β-estradiol.…”

Section: Mechanical Stimulationmentioning

confidence: 99%

See 1 more Smart Citation

Scl-Ab reverts pro-osteoclastogenic signaling and resorption in estrogen deficient osteocytes

Allison

Holdsworth

McNamara

2020

Preprint

View full text Add to dashboard Cite

Background Neutralising antibodies to sclerostin (Scl-Ab) have shown significant potential to induce bone formation and decrease bone resorption, increase strength and substantially reduce fracture risk in animal studies and clinical trials. Mechanical loading negatively regulates sclerostin expression, and sclerostin has been shown to induce RANKL synthesis in osteocytes. We have recently discovered that osteoblasts and osteocytes alter osteoclastogenic signalling (RANKL/OPG) during estrogen-deficiency, and that osteoblast-induced osteoclastogenesis and resorption are exacerbated. However, it is not known whether estrogen deficient osteocytes exhibit exacerbate osteoclastogenesis. The aims of this study were to (1) establish whether osteocytes induce osteoclastogenesis and bone resorption during estrogen deficiency in vitro (2) investigate whether the sclerostin antibody can revert osteocyte-mediated osteoclastogenesis and resorption by attenuating RANKL/OPG production. Results Using conditioned media and co-culture experiments we found increased osteocyte-induced osteoclastogenesis and bone resorption in estrogen deficient conditions. This is the first study to report that administration of Scl-Ab decreased RANKL/OPG ratio and increased WISP1 expression in osteocytes and reduced osteoclastogenesis and bone resorption in vitro. Conclusions This study provides an enhanced understanding of the biological changes underpinning decreases in bone resorption following Scl-Ab treatment observed in vivo by revealing that Scl-Ab can reduce pro-osteoclastogenic cell signalling between osteocytes and osteoclasts.

show abstract

Section: Mechanical Stimulationmentioning

confidence: 99%

Section: Mechanical Stimulationmentioning

confidence: 99%

Scl-Ab reverts pro-osteoclastogenic signaling and resorption in estrogen deficient osteocytes

Allison

Holdsworth

McNamara

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Osteocytes are the main mechanosensors in bone and are subjected to various forms of mechanical loading [15,77,78]. Therefore to capture the in vivo environment more accurately, all osteocytes were subjected to oscillatory uid ow.…”

Section: Mechanical Stimulationmentioning

confidence: 99%

“…Laminar oscillatory uid ow was applied to OCY454 cells using a parallel plate system, which comprised of a syringe pump (NE-1600, New Era Pump Systems, Farmingdale, NY, USA), parallel plate chambers and individual media reservoirs connected through gas-permeable silicone tubing (Cole-Parmer, Vernon Hills, IL, USA) [52]. The OFF loading regime subjected the OCY454 cells to a shear stress of 1 Pa at 0.5 Hz for 1 h, which is within the range of shear stresses experiences by osteocytes in vivo [77,[79][80][81]. Before and after oscillatory uid ow, slides were rinsed with PBS (x3) to remove residual media, to ensure that conditioned media collected did not contain 17β-estradiol.…”

Section: Mechanical Stimulationmentioning

confidence: 99%

Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes 

Allison

Holdsworth

McNamara

2020

Preprint

View full text Add to dashboard Cite

Neutralising antibodies to sclerostin (Scl-Ab) have shown significant potential to induce bone formation and decrease bone resorption, increase strength and substantially reduce fracture risk in animal studies and clinical trials. Mechanical loading negatively regulates sclerostin expression, and sclerostin has been shown to induce RANKL synthesis in osteocytes. However, how Scl-Ab governs osteocyte regulation of osteoclast differentiation and function is not fully understood. We have recently discovered that osteoblasts and osteocytes alter osteoclastogenic signalling (RANKL/OPG) during estrogen-deficiency, and that osteoblast-induced osteoclastogenesis and resorption are exacerbated. However, it is not known whether estrogen deficient osteocytes exhibit exacerbate osteoclastogenesis. The aims of this study were to (1) establish whether osteocytes induce osteoclastogenesis and bone resorption during estrogen deficiency in vitro (2) investigate whether the sclerostin antibody can revert osteocyte-mediated osteoclastogenesis and resorption by attenuating RANKL/OPG expression.Results Using conditioned media and co-culture experiments we found increased osteocyte-induced osteoclastogenesis and bone resorption in estrogen deficient conditions. This is the first study to report that administration of Scl-Ab has the ability to revert osteocyte-mediated osteoclastogenesis and resorption by decreasing RANKL/OPG ratio expression and increasing WISP1 expression in estrogen deficient osteocytes. ConclusionsThis study provides an enhanced understanding of the biological changes underpinning decreases in bone resorption following Scl-Ab treatment observed in vivo by revealing that Scl-Ab can reduce pro-osteoclastogenic cell signalling between osteocytes and osteoclasts.

show abstract

“…For lamellar bone, mechanics is known to play a crucial role in the orientation of the osteons and osteon morphotypes [13] that results in different proportions of osteons with longitudinal fibers adapted to regions under predominant tension and osteons with slanted fibers adapted to zones under predominant compression respectively [14]. Therefore As bone displays multiple levels of porosities where interstitial fluid can circulate in the vascular porosity, the canaliculi and even small spaces between hydroxyapatite (HAP) platelets and the collagen fibers [15], several in vitro investigations of osteocyte mechanobiology have been made on cultured cells that are subjected to direct physiological shear fluid flow [16][17][18][19][20] of about 0.8 to 3 Pa [21] in parallel plate flow chambers or cells reseeded on different substrates such as collagenous hydrogels mimicking osteid [22,23] or various biomaterials scaffolds [24][25][26][27][28] in 3D perfusion bioreactors to produce shear flow stimulation. In 3D bioreactors, cells in animal bone explants have also been directly studied [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Human Stem Cell Derived Osteocytes in Bone-on-Chip

et al. 2018

View full text Add to dashboard Cite

Human mesenchymal stem cells were reseeded in decellularized human bone subject to a controlled mechanical loading to create a bone-on-chip that was cultured for over 26 months. The cell morphology and their secretome were characterized using immunohistochemistry and in situ immunofluorescence under confocal microscopy. The presence of stem cell derived osteocytes was confirmed at 547 days. Different cell populations were identified. Some cells were connected by long processes and formed a network. Comparison of the MSCs in vitro reorganization and calcium response to in situ mechanical stimulation were compared to MLOY4 cells reseeded on human bone. The bone-on-chip produced an ECM of which the strength was nearly a quarter of native bone after 109 days and that contained calcium minerals at 39 days and type I collagen at 256 days. The cytoplasmic calcium concentration variations seemed to adapt to the expected in vivo mechanical load at the successive stages of cell differentiation in agreement with studies using fluid shear flow stimulation. Some degree of bone-like formation over a long period of time with the formation of a newly formed matrix was observed.

show abstract

A model for the role of integrins in flow induced mechanotransduction in osteyocytes

Cited by 11 publications

References 8 publications

Scl-Ab reverts pro-osteoclastogenic signaling and resorption in estrogen deficient osteocytes

Scl-Ab reverts pro-osteoclastogenic signaling and resorption in estrogen deficient osteocytes

Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes

Human Stem Cell Derived Osteocytes in Bone-on-Chip

Contact Info

Product

Resources

About

A model for the role of integrins in flow induced mechanotransduction in osteyocytes

Cited by 11 publications

References 8 publications

Scl-Ab reverts pro-osteoclastogenic signaling and resorption in estrogen deficient osteocytes

Scl-Ab reverts pro-osteoclastogenic signaling and resorption in estrogen deficient osteocytes

Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes&nbsp;

Human Stem Cell Derived Osteocytes in Bone-on-Chip

Contact Info

Product

Resources

About

Scl-Ab reverts pro-osteoclastogenic signalling and resorption in estrogen deficient osteocytes