Molecular regulation of mechanotransduction

Iqbal, Jameel; Zaidi, Mone

doi:10.1016/j.bbrc.2004.12.087

Cited by 199 publications

(141 citation statements)

References 24 publications

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“…The subchondral bone is composed of a specialized connective tissue formed by a mineralized matrix containing the specific collagen type I, proteoglycans and various growth factors and cytokines as well as the bone specific cell types, osteoblasts, osteoclasts and osteocytes [7][8][9]. Osteoblasts and osteoclasts contribute either alone or in combination to bone remodelling, and the disturbance between the activities of these two cell types is responsible for the development of an altered bone metabolism.…”

Section: Introductionmentioning

confidence: 99%

Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors

Tat

Pelletier

Lajeunesse

et al. 2008

Bone

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Background-Osteoarthritis (OA) is the most common human joint disease. Recent studies suggest that an abnormal subchondral bone metabolism is intimately involved in the genesis of this disease. Bone remodelling is tightly regulated by a molecular triad composed of OPG/RANK/ RANKL. RANKL exists as 3 isoforms: RANKL1, 2, and 3. RANKL1 and 2 enhance osteoclastogenesis whereas RANKL3 inhibits this phenomenon. We previously reported that human OA subchondral bone osteoblasts can be discriminated into two subgroups according to their level of PGE 2 [low (L) or high (H)]. Moreover, we also showed that L-OA osteoblasts express higher levels of total RANKL compared to H-OA osteoblasts. In this study, we investigated the level of membranous RANKL, comparing L-and H-OA subchondral bone osteoblasts, as well as its modulation by osteotropic factors. The impact of the modulation of RANKL1 and 3 on the membranous RANKL level was also studied.

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Section: Introductionmentioning

confidence: 99%

Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors

Tat

Pelletier

Lajeunesse

et al. 2008

Bone

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“…EphB4 receptor levels in L-OA osteoblasts were significantly up-regulated by prostaglandin E 2 (PGE 2 ) and interleukin-17 (IL-17). Ephrin B2, PGE 2 , and IL-17 significantly inhibited bone resorption activity in these cells. EphB4 activation by ephrin B2 significantly inhibited the expression of IL-1␤, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-9, MMP-13, and RANKL, but not MMP-2 and osteoprotegerin.…”

mentioning

confidence: 84%

“…Subchondral bone is made up of a specialized connective tissue formed by a mineralized matrix containing the specific type I collagen, proteoglycans, and several growth factors and cytokines, as well as bonespecific cell types (osteoblasts, osteocytes, and osteoclasts) (1,2). Osteoblast and osteoclast activities, either alone or in combination, contribute to the bone remodeling process, and any disturbance in the activities of these 2 cells is responsible for the development of altered bone metabolism.…”

mentioning

confidence: 99%

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Tat¹,

Pelletier²,

Amiable³

et al. 2008

Arthritis & Rheumatism

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Objective. Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having proformation properties. The purpose of this study was to investigate the importance of the ephrin system in OA subchondral bone osteoblasts.Methods. The presence of the EphB4 receptor was determined by immunohistochemistry, and its expression level, modulation upon treatment, and consequences of activation by ephrin B2 were determined by quantitative polymerase chain reaction. The effects of ephrin B2 activation of the EphB4 receptor on bone resorption activity were also determined. EphB4 receptor activation signaling pathways were investigated by specific enzyme-linked immunosorbent assay.Results. EphB4 receptors were present in subchondral bone osteoblasts and osteocytes. Compared with normal and H-OA osteoblasts, EphB4 receptor expression levels were significantly increased in L-OA osteoblasts, with no difference between normal and H-OA osteoblasts. EphB4 receptor levels in L-OA osteoblasts were significantly up-regulated by prostaglandin E 2 (PGE 2 ) and interleukin-17 (IL-17). Ephrin B2, PGE 2 , and IL-17 significantly inhibited bone resorption activity in these cells. EphB4 activation by ephrin B2 significantly inhibited the expression of IL-1␤, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-9, MMP-13, and RANKL, but not MMP-2 and osteoprotegerin. EphB4 receptor activation significantly inhibited the phosphatidylinositol 3-kinase/Akt pathway.Conclusion. This study is the first to provide evidence that EphB4 receptor activation by ephrin B2 in OA subchondral bone could affect abnormal metabolism in this tissue by inhibiting resorption factors and their activities. Ephrin B2 could be targeted as a specific therapeutic approach in the development of a diseasemodifying OA drug.Subchondral bone is made up of a specialized connective tissue formed by a mineralized matrix containing the specific type I collagen, proteoglycans, and several growth factors and cytokines, as well as bonespecific cell types (osteoblasts, osteocytes, and osteoclasts) (1,2). Osteoblast and osteoclast activities, either alone or in combination, contribute to the bone remodeling process, and any disturbance in the activities of these 2 cells is responsible for the development of altered bone metabolism.The ephrin B molecules (ephrin B1, ephrin B2, and ephrin B3) bind in a specific manner to their EphB

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“…For example, Ca 2+ influx induces tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) to levels that can activate MAPK signaling pathways (Rosen and Greenberg, 1996). Elevated Ca 2+ may enhance calcium/ calmodulin-dependent protein kinase (CAM kinase), which can phosphorylate and activate transcription factors such as c-AMP response element-binding protein (CREB) (Sadoshima and Izumo, 1997;Iqbal and Zaidi, 2005).…”

Section: Cellular Mechanotransductionmentioning

confidence: 99%

Mechanoregulation of gene expression in fibroblasts

Wang

Thampatty

Lin

et al. 2007

Gene

219

184

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Mechanical loads placed on connective tissues alter gene expression in fibroblasts through mechanotransduction mechanisms by which cells convert mechanical signals into cellular biological events, such as gene expression of extracellular matrix components (e.g., collagen). This mechanical regulation of ECM gene expression affords maintenance of connective tissue homeostasis. However, mechanical loads can also interfere with homeostatic cellular gene expression and consequently cause the pathogenesis of connective tissue diseases such as tendinopathy and osteoarthritis. Therefore, the regulation of gene expression by mechanical loads is closely related to connective tissue physiology and pathology. This article reviews the effects of various mechanical loading conditions on gene regulation in fibroblasts and discusses several mechanotransduction mechanisms. Future research directions in mechanoregulation of gene expression are also suggested.

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Molecular regulation of mechanotransduction

Cited by 199 publications

References 24 publications

Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors

Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factors

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Mechanoregulation of gene expression in fibroblasts

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