Stimulatory actions of lysophosphatidic acid on mouse ATDC5 chondroprogenitor cells

Itoh, Roichi; Miura, Shigenori; Takimoto, Atsushi; Kondo, Shunya; Sano, Hiroko; Hiraki, Yuji

doi:10.1007/s00774-010-0184-1

Cited by 7 publications

(3 citation statements)

References 48 publications

(26 reference statements)

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“…However, more work is needed to elucidate the mechanism of these effects due to the pleiotropic effects of LPA, such as stimulating cellular proliferation, migration, and survival. [59][60][61] Lastly, morphogens such as TGFb superfamily member BMP7 have been shown to interact with the cytoskeleton by increasing the expression of cytoskeletal proteins in articular chondrocytes in a context-dependent manner. 31 Specifically, BMP7 upregulated cytoskeletal proteins talin and paxillin in monolayer, but not suspension cultures.…”

mentioning

confidence: 99%

Transforming Growth Factorβ-Induced Superficial Zone Protein Accumulation in the Surface Zone of Articular Cartilage Is Dependent on the Cytoskeleton

McNary

Athanasiou

Reddi

2014

Tissue Engineering Part A

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The phenotype of articular chondrocytes is dependent on the cytoskeleton, specifically the actin microfilament architecture. Articular chondrocytes in monolayer culture undergo dedifferentiation and assume a fibroblastic phenotype. This process can be reversed by altering the actin cytoskeleton by treatment with cytochalasin. Whereas dedifferentiation has been studied on chondrocytes isolated from the whole cartilage, the effects of cytoskeletal alteration on specific zones of cells such as superficial zone chondrocytes are not known. Chondrocytes from the superficial zone secrete superficial zone protein (SZP), a lubricating proteoglycan that reduces the coefficient of friction of articular cartilage. A better understanding of this phenomenon may be useful in elucidating chondrocyte dedifferentiation in monolayer and accumulation of the cartilage lubricant SZP, with an eye toward tissue engineering functional articular cartilage. In this investigation, the effects of cytoskeletal modulation on the ability of superficial zone chondrocytes to secrete SZP were examined. Primary superficial zone chondrocytes were cultured in monolayer and treated with a combination of cytoskeleton modifying reagents and transforming growth factor β (TGFβ) 1, a critical regulator of SZP production. Whereas cytochalasin D maintains the articular chondrocyte phenotype, the hallmark of the superficial zone chondrocyte, SZP, was inhibited in the presence of TGFβ1. A decrease in TGFβ1-induced SZP accumulation was also observed when the microtubule cytoskeleton was modified using paclitaxel. These effects of actin and microtubule alteration were confirmed through the application of jasplakinolide and colchicine, respectively. As Rho GTPases regulate actin organization and microtubule polymerization, we hypothesized that the cytoskeleton is critical for TGFβ-induced SZP accumulation. TGFβ-mediated SZP accumulation was inhibited by small molecule inhibitors ML141 (Cdc42), NSC23766 (Rac1), and Y27632 (Rho effector Rho Kinase). On the other hand, lysophosphatidic acid, an upstream activator of Rho, increased SZP synthesis in response to TGFβ1. These results suggest that SZP production is dependent on the functional cytoskeleton, and Rho GTPases contribute to SZP accumulation by modulating the actions of TGFβ.

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confidence: 99%

Transforming Growth Factorβ-Induced Superficial Zone Protein Accumulation in the Surface Zone of Articular Cartilage Is Dependent on the Cytoskeleton

McNary

Athanasiou

Reddi

2014

Tissue Engineering Part A

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“…In osteoclasts, LPA acts through multiple receptor subtypes to elevate intracellular Ca 2+ (Ca 2+ i ), induce cellular retraction, activates nuclear factor of activated T cell 1 (NFAT1) and prolongs osteoclast survival [307]. Undifferentiated and differentiated ATDC5 chondroprogenitor cells were found to express LPA [308]. …”

Section: Phospholipases A2mentioning

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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“…Lysophosphatidic acids (LPAs) such as GP18:0 can act via membrane bound G-protein coupled receptors and have been shown to regulate the mitogen activated protein kinases (MAPKs), more specifically extracellular signal-regulated kinase (ERK) pathways that are central in cell growth and differentiation 38 . Further, there is emerging evidence that murine cartilaginous bone mesenchymal cells express LPA receptors and that LPAs can have effects on chondroprogenitor activation as seen in the ATDC5 cell line 39 and in primary murine chondrocytes 40 .…”

Section: Identification Of Candidate Biological Moleculesmentioning

confidence: 99%

Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures

Alakpa¹,

Jayawarna²,

Lampel³

et al. 2016

Chem

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Abstract. Stem cells are known to differentiate in response toHowever, identification of these stem cell inducing molecules is non-trivial and rational approaches to discover drugs for achieving reproducible, targeted stem cell control remain elusive. Here, we demonstrate the design of supramolecular hydrogels that allow targeting of a range of stem cell phenotypes, providing a useful platform for discovery of differentiation inducing metabolites. These gels are simple in composition, containing a fibre forming aromatic peptide amphiphile, which is coassembled with a surfactant-like amphiphile that provides hydrophilic surface functionality to the fibres. The stiffness of the gels can be precisely tuned over the entire range that is typically associated with stem cell differentiation (0.1-40 kPa). 3We demonstrate that the gels can be used to direct stem cell differentiation without the need for induction media and they are therefore ideally suited to study stem cell behaviour -including as drug discovery platforms. To achieve this, we study the cell's usage of biological small molecules, metabolites, during differentiation and select bioactive metabolites that can target bone and cartilage formation specifically. This new use of designed supramolecular biomaterials can be envisaged to remove serendipity from discovery of metabolites associated with biological processes as drug candidates. Introduction.

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Stimulatory actions of lysophosphatidic acid on mouse ATDC5 chondroprogenitor cells

Cited by 7 publications

References 48 publications

Transforming Growth Factorβ-Induced Superficial Zone Protein Accumulation in the Surface Zone of Articular Cartilage Is Dependent on the Cytoskeleton

Transforming Growth Factorβ-Induced Superficial Zone Protein Accumulation in the Surface Zone of Articular Cartilage Is Dependent on the Cytoskeleton

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

Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures

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