Peroxisome proliferator-activated receptor gamma in osteoarthritis

Fahmi, Hassan; Martel‐Pelletier, Johanne; Pelletier, Jean‐Pierre; Kapoor, Mohit

doi:10.1007/s10165-010-0347-x

Cited by 45 publications

(32 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is worth noting that OPTN is highly expressed in the brain, retina and skeletal muscle. In addition VDR and PPARG are known regulators of bone and cartilage metabolism [27,28].…”

Section: Discussionmentioning

confidence: 99%

Genetic association study of UCMA/GRP and OPTN genes (PDB6 locus) with Paget's disease of bone

Michou

Conceição

Morissette

et al. 2012

Bone

View full text Add to dashboard Cite

We performed a genetic association study of rare variants and single nucleotide polymorphisms (SNPs) of UCMA/GRP and OPTN genes, in French-Canadian patients with Paget's disease of bone (PDB) and in healthy controls from the same population. We reproduced the variant found in the UCMA/GRP basal promoter and tested its functionality using in vitro transient transfection assays. Interestingly, this SNP rs17152980 appears to affect the transcription level of UCMA/ GRP. In addition, we have identified five rare genetic variants in UCMA/GRP gene, four of them being population-specific, although none were found to be associated with PDB. Six Tag SNPs of UCMA/GRP gene were associated with PDB, particularly the SNP rs17152980 (uncorrected P=3.8 × 10 −3 ), although not significant after Bonferroni's correction. More importantly, we replicated the strong and statistically significant genetic association of two SNPs of the OPTN gene, the rs1561570 (uncorrected P=5.7 × 10 −7 ) and the rs2095388 (uncorrected P=4.9 × 10 −3 ), with PDB. In addition, we identified a very rare variant found to be located close to the basal promoter of the OPTN gene, at −232 bp from its distal transcription start site. Furthermore, depending on the type of allele present (G or A), the binding of several important nuclear factors such as the vitamin D or the retinoic acid receptors is predicted to be altered at this position, suggesting a significant effect in the regulation of transcription of the OPTN gene. In conclusion, we identified a functional SNP located in the basal promoter of the UCMA/GRP gene which provided a weak genetic association with PDB. In addition, we replicated the strong genetic association of two already known SNPs of the OPTN gene, with PDB in a founder effect population. We also identified a very rare variant in the promoter of OPTN, and through Joint corresponding authors: Laëtitia Michou, Rhumatologie-S763, CHUQ-CHUL, 2705 boulevard Laurier,

show abstract

“…It is worth noting that OPTN is highly expressed in the brain, retina and skeletal muscle. In addition VDR and PPARG are known regulators of bone and cartilage metabolism [27,28].…”

Section: Discussionmentioning

confidence: 99%

Genetic association study of UCMA/GRP and OPTN genes (PDB6 locus) with Paget's disease of bone

Michou

Conceição

Morissette

et al. 2012

Bone

View full text Add to dashboard Cite

show abstract

“…Modulation of PPARs, especially PPAR and PPAR / , also has the potential to resolve inflammation. PPAR ligands are therefore of growing interest for the possible treatment of inflammatory diseases such as osteoarthritis, diabetic and autoimmune nephritis, chronic bowel disease, and psoriasis [7,[249][250][251]]. …”

Section: Anti-inflammatory Profile Of Ppar Ligandsmentioning

confidence: 99%

Biology and Therapeutic Applications of Peroxisome Proliferator- Activated Receptors

Menéndez-Gutierrez

Röszer²,

Ricote

2012

CTMC

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPARs) are ligand dependent transcription factors. The three mammalian PPARs are key regulators of fatty acid and lipoprotein metabolism, glucose homeostasis, cellular proliferation/ differentiation and the immune response. PPARs are therefore important targets in the treatment of metabolic disorders such as insulin resistance and type 2 diabetes mellitus, and are also of interest in relation to chronic inflammatory diseases such as atherosclerosis, arthritis, chronic pulmonary inflammation, pancreatitis, inflammatory bowel disease, and psoriasis. Recent advances have attributed novel functions to PPARs in blood pressure regulation, neuroinflammation, nerve-cell protection, inflammatory pain reduction, and the hypothalamic control of metabolism. The abundant pleiotropic actions of PPARs suggest that PPAR agonists have enormous therapeutic potential. However, current PPAR-based therapies often have undesired side effects due to the concomitant activation of PPARs in non-target cells. There is therefore growing interest in the development of cell-specific PPAR agonists and improvement of the clinical use of PPAR ligands. This review gives an overview of PPAR functions and discusses the current and potential medical implications of PPAR ligands in various pathologies, ranging from metabolic disorders to cardiovascular disease, chronic inflammation, neurodegenerative disorders and cancer.

show abstract

“…C) ROLE OF PPAR␥ IN DEVELOPMENT OF JOINT DISORDERS. A possible role of PPAR␥ in the development of OA has been recently suggested (112). In cultured chondrocytes from OA patients, PPAR␥ activation by 15d-PGJ 2 or Tro was shown to suppress IL-1␤-induced production of NO and PGE 2 through attenuation of expression of their respective synthases, iNOS and COX-2 (40, 111,113).…”

Section: Ppar␥mentioning

confidence: 97%

Nuclear Receptors in Bone Physiology and Diseases

Imai

Youn

Inoue

et al. 2013

Physiological Reviews

View full text Add to dashboard Cite

During the last decade, our view on the skeleton as a mere solid physical support structure has been transformed, as bone emerged as a dynamic, constantly remodeling tissue with systemic regulatory functions including those of an endocrine organ. Reflecting this remarkable functional complexity, distinct classes of humoral and intracellular regulatory factors have been shown to control vital processes in the bone. Among these regulators, nuclear receptors (NRs) play fundamental roles in bone development, growth, and maintenance. NRs are DNA-binding transcription factors that act as intracellular transducers of the respective ligand signaling pathways through modulation of expression of specific sets of cognate target genes. Aberrant NR signaling caused by receptor or ligand deficiency may profoundly affect bone health and compromise skeletal functions. Ligand dependency of NR action underlies a major strategy of therapeutic intervention to correct aberrant NR signaling, and significant efforts have been made to design novel synthetic NR ligands with enhanced beneficial properties and reduced potential negative side effects. As an example, estrogen deficiency causes bone loss and leads to development of osteoporosis, the most prevalent skeletal disorder in postmenopausal women. Since administration of natural estrogens for the treatment of osteoporosis often associates with undesirable side effects, several synthetic estrogen receptor ligands have been developed with higher therapeutic efficacy and specificity. This review presents current progress in our understanding of the roles of various nuclear receptor-mediated signaling pathways in bone physiology and disease, and in development of advanced NR ligands for treatment of common skeletal disorders.

show abstract

Peroxisome proliferator-activated receptor gamma in osteoarthritis

Cited by 45 publications

References 81 publications

Genetic association study of UCMA/GRP and OPTN genes (PDB6 locus) with Paget's disease of bone

Genetic association study of UCMA/GRP and OPTN genes (PDB6 locus) with Paget's disease of bone

Biology and Therapeutic Applications of Peroxisome Proliferator- Activated Receptors

Nuclear Receptors in Bone Physiology and Diseases

Contact Info

Product

Resources

About