Featured Article: Deficiency of G-protein coupled receptor 40, a lipid-activated receptor, heightens <i>in vitro-</i> and <i>in vivo-</i>induced murine osteoarthritis

Monfoulet, Laurent-Emmanuel; Philippe, Claire; Mercier, Sylvie; Coxam, Véronique; Wittrant, Yohann

doi:10.1177/1535370214565078

Cited by 13 publications

(9 citation statements)

References 45 publications

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“…Furthermore, Gpr40 downregulation protects osteocytes from apoptosis. 374 Wauquier et al 43 observed that Gpr40 −/− mice had a reduction in BMD and bone mass with higher promoting osteoclast differentiation, and Monfoulet et al 375 observed a more severe OA-induced phenotype in Gpr40 −/− mice, marked by elevated tidemark exposure, osteophyte formation, and subchondral bone sclerosis (Table 9).…”

Section: Diseases or Dysfunction Caused By Gpcr Mutation Or Deletion mentioning

confidence: 99%

The role of GPCRs in bone diseases and dysfunctions

et al. 2019

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The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals. Critical roles of GPCRs have been established in bone development, remodeling, and disease. Multiple human GPCR mutations impair bone development or metabolism, resulting in osteopathologies. Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals. To date, 92 receptors (5 glutamate family, 67 rhodopsin family, 5 adhesion, 4 frizzled/taste2 family, 5 secretin family, and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals). By analyzing data from these 92 GPCRs, we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions, and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models. Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD: 9 genes each for human height and osteoporosis; 4 genes each for human osteoarthritis (OA) and fracture risk; and 2 genes each for adolescent idiopathic scoliosis (AIS), periodontitis, osteosarcoma growth, and tooth development. Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass, while deficiency of 22 GPCRs increased bone mass and BMD; deficiency of 8 GPCRs reduced body length, while 5 mice had reduced femur size upon GPCR deletion. Furthermore, deficiency in 6 GPCRs induced osteoporosis; 4 induced osteoarthritis; 3 delayed fracture healing; 3 reduced arthritis severity; and reduced bone strength, increased bone strength, and increased cortical thickness were each observed in 2 GPCR-deficiency models. The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis, population studies, and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.

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Section: Diseases or Dysfunction Caused By Gpcr Mutation Or Deletion mentioning

confidence: 99%

The role of GPCRs in bone diseases and dysfunctions

et al. 2019

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“…Chondrocytes express membrane receptors both for FAs and lipoproteins, including GPR40 and GPR120, TLR4, and CD36, as well as some members of the LDLR and LRP families . Global knockout of GPR40 has been shown to increase predisposition to injury‐induced OA in a mouse model and, when challenged with interleukin 1 beta (IL‐1β), the GPR40 −/− chondrocyte produced more inflammatory molecules, such as IL‐6, PGE 2 , MMP‐2, and MMP‐9, compared with wild‐type cells . Interestingly, Dehne and coworkers reported that GPR40 is upregulated in human OA chondrocytes .…”

Section: Cartilage and Fatty Acidsmentioning

confidence: 99%

Physiologic and pathologic effects of dietary free fatty acids on cells of the joint

Harasymowicz

Dicks

et al. 2019

Annals of the New York Academy of Sciences

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Fatty acids (FAs) are potent organic compounds that not only can be used as an energy source during nutrient deprivation but are also involved in several essential signaling cascades in cells. Therefore, a balanced intake of different dietary FAs is critical for the maintenance of cellular functions and tissue homeostasis. A diet with an imbalanced fat composition creates a risk for developing metabolic syndrome and various musculoskeletal diseases, including osteoarthritis (OA). In this review, we summarize the current state of knowledge and mechanistic insights regarding the role of dietary FAs, such as saturated FAs, omega-6 polyunsaturated FAs (PUFAs), and omega-3 PUFAs on joint inflammation and OA pathogeneses. In particular, we review how different types of dietary FAs and their derivatives distinctly affect a variety of cells within the joint, including chondrocytes, osteoblasts, osteoclasts, and synoviocytes. Understanding the molecular mechanisms underlying the effects of FAs on metabolic behavior, anabolic, and catabolic processes, as well as the inflammatory response of joint cells, may help identify therapeutic targets for the prevention of metabolic joint diseases.

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“…Recently, we demonstrated in vivo and in vitro the implication of this receptor in bone homeostasis . GPR40 −/− mice were characterized by an osteopenic/osteoporotic phenotype when compared to wild‐type (WT) littermates.…”

Section: Introductionmentioning

confidence: 99%

GPR40 mediates potential positive effects of a saturated fatty acid enriched diet on bone

Philippe

Wauquier

Landrier

et al. 2016

Molecular Nutrition Food Res

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Scope:The stimulation of the free fatty acid receptor G-protein coupled receptor (GPR) 40 by GW9508 prevents bone loss by inhibiting osteoclast activity, both in vitro and in vivo. Here, we questioned whether the stimulation of the GPR40 receptor by dietary fatty acids may lead to the same beneficial effect on bone. Methods and results:We investigated (i) the impact of a fatty acid enriched diet (high-fat diet [HFD]) on bone health in C57/BL6 female mice depending on (ii) the estrogen status (ovariectomy) and (iii) the genotype (GPR40 +/+ or GPR40 −/− ). Bone mineral density (BMD), body composition, weight, inflammation and bone remodeling parameters were monitored. HFD decreased BMD in HFD-SH-GPR40 +/+ mice but OVX failed to further impact BMD in HFD-OVX-GPR40 +/+ mice, while additional bone loss was observed in HFD-OVX-GPR40 −/− animals. These data suggest that when stimulated by fatty acid enriched diets GPR40 contributes to counteract ovariectomy-induced bone alteration. The sparing effect is supported by the modulation of both the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio in blood stream and the expression level of inflammatory markers in adipose tissues. Bone preservation by GPR40 stimulation is dependent on the presence of long-chain saturated fatty acids. Conclusion: GPR40 contributes to counter ovariectomy-induced bone loss in a context of saturated fatty acid enrichment. Keywords:Free fatty acid receptor / GPR40 / High-fat diet / Nutrition / Osteoporosis Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Dr. Yohann Wittrant E-mail: yohann.wittrant@clermont.inra.fr Abbreviations: ANOVA, analysis of variance; BMD, bone mineral density; GPR, G-protein coupled receptor; HFD, high-fat diet; MCP-1, monocyte chemoattractant protein 1; OPG, osteoprotegerin; RANKL, receptor activator of nuclear factor kappa-B ligand

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Featured Article: Deficiency of G-protein coupled receptor 40, a lipid-activated receptor, heightens in vitro- and in vivo-induced murine osteoarthritis

Cited by 13 publications

References 45 publications

The role of GPCRs in bone diseases and dysfunctions

The role of GPCRs in bone diseases and dysfunctions

Physiologic and pathologic effects of dietary free fatty acids on cells of the joint

GPR40 mediates potential positive effects of a saturated fatty acid enriched diet on bone

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