Would increased interstitial fluid flow through in situ mechanical stimulation enhance bone remodeling?

Letechipia, Jorge; Montero, Aldo Alessi; Rodríguez, Gerardo; Asbún, Juan

doi:10.1016/j.mehy.2010.02.021

Cited by 14 publications

(9 citation statements)

References 49 publications

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“…When the chemical method (CoCl 2 ) was used to simulate the hypoxic environment in vitro, the proliferative activity of MLO-Y4 cells was first detected to avoid the effects of apoptosis (Figure S1), because apoptotic bodies released by apoptotic osteocytes expresses a mass of RANKL to recruit osteoclast precursors and differentiation (Al-Dujaili et al, 2011). We chose 100 μmol/L CoCl 2 (Figure S1) and 2% O 2 what concentration was the most commonly used as the experimental concentration as hypoxic stimulus (Arnett et al, 2003 Membrane-bound RANKL plays a crucial role in osteoclastogenesis in the coculture of immediate contact between osteocytes and osteoclast precursors (Letechipia et al, 2010). However, there was no osteoclast formation in the coculture system of MLO-Y4 cells directly contacted with RAW264.7 cells under hypoxia because persistent hypoxia to the coculture system led massive cell to death (Knowles & Athanasou, 2009).…”

Section: Discussionmentioning

confidence: 99%

HIF‐1α facilitates osteocyte‐mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro

Zhu

Tang

et al. 2019

Journal Cellular Physiology

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Osteocytes, entrapped within the mineralized bone matrix, has been found to have numerous functions such as acting as an orchestrator of bone remodeling through regulation of both osteoclast and osteoblast activity and also functioning as an endocrine cell. Due to a specialized morphology and surrounding structure, osteocytes are more tolerant to hypoxia during osteoporosis, fracture, osteoarthritis, and orthodontic-orthognathic combination therapy. Hypoxia-inducible factor-1α (HIF-1α) is one of the master regulators of hypoxia reactions, playing an important role in bone modeling, remodeling, and homeostasis. This study aimed to investigate the pivotal functional role of HIF-1α in osteocytes initiating of bone remodeling under hypoxia. In the present study, the osteoclasts formation induced by RAW264.7 was significantly promoted in conditioned media (CM) from osteocytic MLO-Y4 exposed to hypoxia in vitro. Therefore, hypoxic MLO-Y4 cells simulated by 100 μmol/L CoCl 2 or 2% O 2 stably expressed HIF-1α proteins and upregulated the expression of receptor activator of nuclear factor-κB ligand (RANKL) at both the messenger RNA (mRNA) and protein level. Furthermore, with the Knockdown of HIF-1α, the expression of RANKL mRNA and protein decreased after transient transfection. In addition, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription (STAT3) was also correlated with HIF-1α and RANKL levels under hypoxia. Then AG490, a JAK2 inhibitor, inhibited p-JAK2, p-STAT3 and RANKL expression. It was possible that AG490 disturbed the contact of HIF-1α and RANKL by JAK2/STAT3 pathway, influencing osteoclastogenesis. Our findings suggested that HIF-1α promoted the expression of RANKL by activating JAK2/STAT3 pathway in MLO-Y4 cells, and enhanced osteocyte-mediated osteoclastic differentiation in vitro. K E Y W O R D Shypoxia-inducible factor-1α, JAK2/STAT3 pathway, osteoclastogenesis, osteocyte, receptor activator of nuclear factor-κB

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Section: Discussionmentioning

confidence: 99%

HIF‐1α facilitates osteocyte‐mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro

Zhu

Tang

et al. 2019

Journal Cellular Physiology

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“…One of the proposed mechanisms by which osteocytes sense mechanical load is through interstitial fluid flow through the lacunae-canaliculi network—for two mechanosensory reviews in this issue, see [89, 90]—which causes a shear stress on the cells [91]. Fluid flow shear stress in MLO-Y4 cells induces prostaglandin E 2 (PGE 2 ) and increases the number of gap junctions and the expression of the gap junction protein connexin 43 (Cx43) [92].…”

Section: Wnt Signaling In Osteocytes and Related Bone Therapiesmentioning

confidence: 99%

Regulation of Wnt/β-catenin signaling within and from osteocytes

Burgers¹,

Williams²

2013

Bone

136

120

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Bone has long been known to be responsive to mechanical loading. For at least 25 years it has been known that osteocytes sense mechanical load, and because of their response to mechanical loading, osteocytes are believed to be the mechanosensory cell. The Wnt/β-catenin signaling pathway has been shown to be crucial in bone development. Mutations in LRP5 and SOST, which cause high bone mass, have increased interest in the Wnt pathway as a potential target for osteoporosis therapy and have helped link Wnt/β-catenin signaling to bone’s response to mechanical loading. Because of its specificity to osteocytes, the Wnt inhibitor sclerostin is a target for anabolic bone therapies. The response of bone to mechanical loading is critically regulated by osteocytes secreting sclerostin, which binds to Lrp5.

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“…The magnitude of fl uid fl ow stress in bone tissue is thought to be between 0.8 and 3.0 Pa in vivo (Weinbaum et al, 1994). In vitro, primary mechanosensors, osteocytes and osteoblasts have been used to investigate the morphological and functional responses to fl uid shear stresses (Barron et al, 2010;Letechipia et al, 2010). As well, in the past twenty years there have been many important developments in mechanotransduction (Reich and Frangos, 1993), (Jiang and Cheng, 2001).…”

Section: Introductionmentioning

confidence: 99%

Oscillatory fluid flow elicits changes in morphology, cytoskeleton and integrin-associated molecules in MLO-Y4 cells, but not in MC3T3-E1 cells

Zhang

et al. 2012

Biol. Res.

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Interstitial fl uid fl ow stress is one of the most important mechanical stimulations of bone cells under physiological conditions. Osteocytes and osteoblasts act as primary mechanosensors within bones, and in vitro are able to respond to fl uid shear stress, both morphologically and functionally. However, there is little information about the response of integrin-associated molecules using both osteoblasts and osteocytes. In this study, we investigated the changes in response to 2 hours of oscillatory fl uid fl ow stress in the MLO-Y4 osteocyte-like cell line and the MC3T3-E1 osteoblast-like cell line. MLO-Y4 cells exhibited a signifi cant increase in the expression of integrin-associated molecules, including OPN, CD44, vinculin and integrin αvβ3. However, there was no or limited increase observed in MC3T3-E1 osteoblast-like cells. Cell area and fi ber stress formation were also markedly promoted by fl uid fl ow only in MLO-Y4 cells. But the numbers of processes per cell remain unaff ected in both cell lines.

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Would increased interstitial fluid flow through in situ mechanical stimulation enhance bone remodeling?

Cited by 14 publications

References 49 publications

HIF‐1α facilitates osteocyte‐mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro

HIF‐1α facilitates osteocyte‐mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro

Regulation of Wnt/β-catenin signaling within and from osteocytes

Oscillatory fluid flow elicits changes in morphology, cytoskeleton and integrin-associated molecules in MLO-Y4 cells, but not in MC3T3-E1 cells

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