Effects of sphingosine-1-phosphate and lysophosphatidic acid on human osteoblastic cells

Dziak, Rosemary; Yang, Baoye; Leung, Betty; Li, S; Marzec, N.; Margarone, Joseph E.; Bobek, Libuse A.

doi:10.1016/s0952-3278(02)00277-6

Cited by 55 publications

(32 citation statements)

References 17 publications

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“…Angiogenesis is thought to temporally precede osteogenesis [52], as predicted by the earliest studies of bone development [49]. To this end, we hypothesize that S1P's observed ability to remodel the microvasculature, as demonstrated in the dorsal skinfold window chamber studies, combined with S1P's reported ability to stimulate migration and proliferation of osteoblast precursor cells [34,53,54], which are critical to the formation of new bone, stimulates the formation of new bone in a model of cranial repair. Further studies are needed to elucidate the relationship between S1P signaling and bone remodeling, but these studies provide firm evidence that S1P-induced microvascular remodeling is a stimulus for the enhanced tissue-engineered healing of osseous defects.…”

Section: Discussionmentioning

confidence: 86%

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

et al. 2008

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Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that impacts migration, proliferation, and survival in diverse cells types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. In this study, we investigated the effects of sustained release of S1P on microvascular remodeling and associated bone defect healing in vivo. The murine dorsal skinfold window chamber model was used to evaluate the structural remodeling response of the microvasculature. Our results demonstrated that 1:400 (w/w) loading and subsequent sustained release of S1P from poly(lactic-coglycolic acid) (PLAGA) significantly enhanced lumenal diameter expansion of arterioles and venules after 3 and 7 days. Incorporation of 5-bromo-2-deoxyuridine (BrdU) at day 7 revealed significant increases in mural cell proliferation in response to S1P delivery. Additionally, three-dimensional (3D) scaffolds loaded with S1P (1:400) were implanted into critical-size rat calvarial defects and healing of bony defects was assessed by radiograph x-ray, microcomputed tomography (μCT), and histology. Sustained release of S1P significantly increased the formation of new bone after 2 and 6 weeks of healing and histological results suggest increased numbers of blood vessels in the defect site. Taken together, these experiments support the use of S1P delivery for promoting microvessel diameter expansion and improving the healing outcomes of tissue-engineered therapies.

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Section: Discussionmentioning

confidence: 86%

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

et al. 2008

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“…LPA has been shown previously to have mitogenic and anti-apoptotic effects on rat osteoblasts (32,55). Mitogenic effects of LPA have been confirmed in human osteoblastic cells (33), and it has been reported recently that LPA enhances the motility of a murine osteoblast-like cell line (47). Moreover, Rho and Rho-associated kinase (downstream effectors of LPA1) have been shown to drive mesenchymal stem cells to differentiate into osteoblasts (21).…”

Section: Discussionmentioning

confidence: 94%

“…Scale bars are 10 m. brane blebbing. LPA binds to specific G protein-coupled receptors in a variety of cell types, including rat and human osteoblasts (32,33). In both WT and P2X7 KO cells, LPA (10 M) induced zeiosis similar to that caused by BzATP in WT cells ( Fig.…”

Section: ϩmentioning

confidence: 85%

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P2X7 Nucleotide Receptors Mediate Blebbing in Osteoblasts through a Pathway Involving Lysophosphatidic Acid

Panupinthu

Zhao

Possmayer

et al. 2007

Journal of Biological Chemistry

109

108

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Extracellular nucleotides, released in response to mechanical or inflammatory stimuli, signal through P2 receptors in many cell types, including osteoblasts. P2X7 receptors are ATP-gated cation channels that can induce formation of large membrane pores. Disruption of the gene encoding the P2X7 receptor leads to decreased periosteal bone formation and insensitivity of the skeleton to mechanical stimulation. Our purpose was to investigate signaling pathways coupled to P2X7 activation in osteoblasts. Live cell imaging showed that ATP or 2,3-O-(4-benzoylbenzoyl)-ATP (BzATP), but not UTP, UDP, or 2-methylthio-ADP, induced dynamic membrane blebbing in calvarial osteoblasts. Blebbing was observed in calvarial cells from wildtype but not P2X7 knock-out mice. P2X7 receptors coupled to activation of phospholipase D and A 2 , inhibition of which suppressed BzATP-induced blebbing. Activation of these phospholipases leads to production of lysophosphatidic acid (LPA). LPA caused dynamic blebbing in osteoblasts from both wild-type and P2X7 knock-out mice, similar to that induced by BzATP in wildtype cells. However, LPA-induced blebbing was more rapid in onset and was not affected by inhibition of phospholipase D or A 2 . Blockade or desensitization of LPA receptors suppressed blebbing in response to LPA and BzATP, without affecting P2X7-stimulated pore formation. Thus, LPA functions downstream of P2X7 receptors to induce membrane blebbing. Furthermore, inhibition of Rho-associated kinase abolished blebbing induced by both BzATP and LPA. In summary, we propose a novel signaling axis that links P2X7 receptors through phospholipases to production of LPA and activation of Rho-associated kinase. This pathway may contribute to P2X7-stimulated osteogenesis during skeletal development and mechanotransduction.

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“…LPA and related lipids, lysophosphatidylcholine (LPC), sphingosine-1-phosphate (S1P) and the structurally related S1P receptor agonist prodrug, FTY720 (Fingolimod), are assuming a growing significance in mineralising tissue biology (Blackburn and www.ecmjournal.org JP Mansell et al Lysophospholipid bio-functionalisation of titanium Mansell, 2012); LPC is a major circulating lipid precursor to LPA that has recently been reported to induce the transdifferentiation of human aortic smooth muscle cells to the osteoblast phenotype (Vickers et al, 2010). Both LPA and S1P have been identified as stimulating both human osteoblasts (Dziak et al, 2003;Gidley et al, 2006;Grey et al, 2002;Mansell et al, 2009b;Mansell et al, 2010) and their bone marrow progenitors. It has been proposed that these lipids likely aid cell migration and survival, key events to securing tissue repair/regeneration (P'ebay et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Lysophosphatidic acid-functionalised titanium as a superior surface for supporting human osteoblast (MG63) maturation

Mansell¹,

Brown²,

Knapp³

et al. 2012

eCM

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Covalent modifications of titanium with small molecules known to promote human osteoblast maturation are especially attractive in developing superior biomaterials. An important step in securing competent bone formation at implant sites is promoting the formation of mature osteoblasts, either from committed pre-osteoblasts or from their mesenchymal progenitors. To this end our research has focussed on identifying molecules that enhance human osteoblast formation and maturation and to develop ways of covalently attaching these molecules to implant surfaces so that they are more likely to withstand the rigors of the implantation process whilst still retaining their bioactivity. Herein we report the novel production of lipid-functionalised titanium using lysophosphatidic acid or a related compound, (3S) 1-fluoro-3-hydroxy-4-butyl-1-phosphonate. Both lipids were especially effective at co-operating with calcitriol to promote human osteoblast maturation at these modified Ti surfaces in vitro. The novel findings presented offer enticing new developments towards the fabrication of next-generation implant devices with the potential to significantly enhance the osseointegration process and with it improvements in future prosthesis performance and longevity.

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Effects of sphingosine-1-phosphate and lysophosphatidic acid on human osteoblastic cells

Cited by 55 publications

References 17 publications

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering

P2X7 Nucleotide Receptors Mediate Blebbing in Osteoblasts through a Pathway Involving Lysophosphatidic Acid

Lysophosphatidic acid-functionalised titanium as a superior surface for supporting human osteoblast (MG63) maturation

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