Mechanosensitivity of human osteosarcoma cells and phospholipase C β2 expression

Hoberg, Maik; Gratz, Hans-Henning; Noll, Markus; Jones, David B.

doi:10.1016/j.bbrc.2005.05.088

Cited by 21 publications

(18 citation statements)

References 33 publications

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“…Mechanical strain plays a critical role in bone formation (46) ((29, 50) by stimulating osteoblastic activities (29) (24) but also by inducing the production of pro-angiogenic factors such as vascular endothelial growth factor A (VEGF) (57). VEGF in cooperation with the fibroblast growth factor (FGF) family, insulin growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor-A (PDGF-A), and the transforming growth factor-ß (TGF-ß) family, are all involved in bone angiogenesis (19) (40) (16) (25) (12).…”

Section: Introductionmentioning

confidence: 99%

Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation

Faure

Linossier

Malaval

et al. 2008

Bone

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To cite this version:Céline None of the authors has any conflicts of interest. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractSince VEGF-A is involved in mechanically-induced bone gain and because vegf exists under 6 isoforms exerting various biological effects, we studied vegf isoforms expression and VEGF protein production in osteoblastic cells (rat Ros17/2.8 and human osteoblasts) submitted to 4 mechanical regimens. Mechanical regimens (1% stretch deformation)were designed with a fixed number of cycles (450) mRNA expressions of soluble VEGF isoforms (121,165) were specifically expressed under low frequency while matrix-bound VEGF isoforms (206, 189, 165, 145) were specifically expressed under high frequency in human osteoblasts. As F-actin stress fibers formation was significantly increased selectively in high frequencies conditions, we disrupted actin fibers in Ros17/2.8 and found that immobilisation of VEGF was abolished. Conversely, jasplakinolide treatment which increases stress fibers formation was able to mimic high frequency stretch-induced immobilisation of VEGF. Thus, we speculate that the stretchinduced increase in cell tension is responsible for matrix-bound vegf isoform production.Mechanically-induced selection of soluble or matrix-bound VEGF production may modify osteoblast and endothelial c ells crosstalk crucial during osteogenesis and fracture healing.

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Section: Introductionmentioning

confidence: 99%

Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation

Faure

Linossier

Malaval

et al. 2008

Bone

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“…The second enzyme, a GTP-activated PI-4, 5-bisphosphate (PIP 2 )-specific PLC is found in the plasma membranes [403]. PI-PLC-β1, -β3, -γ1, -γ2, and -δ1 were detected by Western blot in osteosarcoma MG-63, MNNG/HOS, OST, U-2/OS, and SaOS-2 cell lines, while PI-PLC-β2 was only expressed in MG-63 and MNNG/HOS cells [404]. PI-PLC-β2 is involved in the mechanotransduction in primary osteoblasts [404].…”

Section: Pi-specific Phospholipase Cmentioning

confidence: 99%

“…PI-PLC-β1, -β3, -γ1, -γ2, and -δ1 were detected by Western blot in osteosarcoma MG-63, MNNG/HOS, OST, U-2/OS, and SaOS-2 cell lines, while PI-PLC-β2 was only expressed in MG-63 and MNNG/HOS cells [404]. PI-PLC-β2 is involved in the mechanotransduction in primary osteoblasts [404]. PLC-γ1 plays an important role in the regulation of cell proliferation and differentiation by generation of the second messengers, DAG, and IP 3 .…”

Section: Pi-specific Phospholipase Cmentioning

confidence: 99%

Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations

Mébarek

Abousalham

Magne

et al. 2013

IJMS

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The present review aims to systematically and critically analyze the current knowledge on phospholipases and their role in physiological and pathological mineralization undertaken by mineralization competent cells. Cellular lipid metabolism plays an important role in biological mineralization. The physiological mechanisms of mineralization are likely to take place in tissues other than in bones and teeth under specific pathological conditions. For instance, vascular calcification in arteries of patients with renal failure, diabetes mellitus or atherosclerosis recapitulates the mechanisms of bone formation. Osteoporosis—a bone resorbing disease—and rheumatoid arthritis originating from the inflammation in the synovium are also affected by cellular lipid metabolism. The focus is on the lipid metabolism due to the effects of dietary lipids on bone health. These and other phenomena indicate that phospholipases may participate in bone remodelling as evidenced by their expression in smooth muscle cells, in bone forming osteoblasts, chondrocytes and in bone resorbing osteoclasts. Among various enzymes involved, phospholipases A1 or A2, phospholipase C, phospholipase D, autotaxin and sphingomyelinase are engaged in membrane lipid remodelling during early stages of mineralization and cell maturation in mineralization-competent cells. Numerous experimental evidences suggested that phospholipases exert their action at various stages of mineralization by affecting intracellular signaling and cell differentiation. The lipid metabolites—such as arachidonic acid, lysophospholipids, and sphingosine-1-phosphate are involved in cell signaling and inflammation reactions. Phospholipases are also important members of the cellular machinery engaged in matrix vesicle (MV) biogenesis and exocytosis. They may favour mineral formation inside MVs, may catalyse MV membrane breakdown necessary for the release of mineral deposits into extracellular matrix (ECM), or participate in hydrolysis of ECM. The biological functions of phospholipases are discussed from the perspective of animal and cellular knockout models, as well as disease implications, development of potent inhibitors and therapeutic interventions.

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“…Activation of focal adhesion kinase (FAK) directs signaling pathway of mechanical strain in osteoblasts 1 . Phospholipase C (PLC) generates inositol trisphosphate and diacylglycerol of the second messengers, playing a pivotal role in the signal transduction of mechanical stress in osteoblasts 2 . The PLC isoforms include PLC‐βs that are activated by interacting with G‐αq subunit of G proteins and PLC‐γs that are activated by tyrosine phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

Small GTPase Ras and Rho Expression in Rat Osteoblasts during Spaceflight

Kumei

Shimokawa

Ohya

et al. 2007

Annals of the New York Academy of Sciences

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Rat osteoblasts were cultured for 4 and 5 days aboard a space shuttle and solubilized after a 24-h treatment with 1alpha,25 dihydroxyvitamin D(3). The quantitative RT-PCR determined the mRNA levels of signaling molecules upstream and downstream Ras. The small GTPase is activated by guanine nucleotide exchange protein (GEF) and deactivated by GTPase-activating protein (GAP). When external stimuli are transduced into intracellular signals, various pathways are recruited: focal adhesion kinase (FAK) is associated with integrin-beta, and directs tyrosine phosphorylation of downstream substrates, including phospholipase C-gamma (PLC-gamma) and son of sevenless (SOS, a Ras GEF). The mRNA levels of FAK and PLC-gamma1 and -gamma2 in the flight cultures were increased 150% and 250% of the ground controls. The SOS mRNA levels in the flight cultures were increased 520% and 320% of the ground controls. Signals via G protein-coupled receptors are transmitted through PLC-beta and Ras GRF (another Ras GEF). Activated Ras then stimulates Raf, mitogen-activated protein kinase (MAPK) cascades. The mRNA levels of Raf, extracellular signal-regulated protein kinase of MAPK family (ERK-1 and -2), and PLC-beta were increased during spaceflight. Rho GAP expression in the flight cultures was increased twofold of the ground controls. Since Rho GAP deactivates Rho, microgravity may suppress Rho signals, regulating actin filament rearrangement. Microgravity signals may involve two pathways (G protein-coupled receptor-mediated pathway and tyrosine phosphorylation-mediated pathway) that activate Ras, Raf, and MAPK cascades in rat osteoblasts.

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Mechanosensitivity of human osteosarcoma cells and phospholipase C β2 expression

Cited by 21 publications

References 33 publications

Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation

Mechanical signals modulated vascular endothelial growth factor-A (VEGF-A) alternative splicing in osteoblastic cells through actin polymerisation

Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations

Small GTPase Ras and Rho Expression in Rat Osteoblasts during Spaceflight

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