Adult Cartilage-Specific Peroxisome Proliferator–Activated Receptor Gamma Knockout Mice Exhibit the Spontaneous Osteoarthritis Phenotype

Vasheghani, Faezeh; Monemdjou, Roxana; Fahmi, Hassan; Zhang, Yue; Pérez, Gemma; Blati, Meryem; St‐Arnaud, René; Pelletier, Jean‐Pierre; Beier, Frank; Martel‐Pelletier, Johanne; Kapoor, Mohit

doi:10.1016/j.ajpath.2012.12.012

Cited by 67 publications

(65 citation statements)

References 36 publications

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“…Rapamycin-induced activation of LC3 increases ULK1, beclin 1, and LC3, promotes chondrocyte survival, decreases synovitis and ADAMTS5 and IL-1β, and prevents glycosaminoglycan loss [85,86]. PPARγ, which has roles in obesity and inflammation, also maintains homeostasis, in part by regulating mTOR [87]…”

Section: Autophagy Cell Survival and Bioenergeticsmentioning

confidence: 99%

Emerging targets in osteoarthritis therapy

Goldring

Bérenbaum

2015

Current Opinion in Pharmacology

150

124

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Osteoarthritis (OA) is a destructive joint disease in which the initiation may be attributed to direct injury and mechanical disruption of joint tissues, but the progressive changes are dependent on active cell-mediated processes that can be observed or inferred during the generally long time-course of the disease. Based on clinical observations and experimental studies, it is now recognized a that it is possible for individual patients to exhibit common sets of symptoms and structural abnormalities due to distinct pathophysiological pathways that act independently or in combination. Recent research that has focused on the underlying mechanisms involving biochemical cross talk among the cartilage, synovium, bone, and other joint tissues within a background of poorly characterized genetic factors will be addressed in this review.

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Section: Autophagy Cell Survival and Bioenergeticsmentioning

confidence: 99%

Emerging targets in osteoarthritis therapy

Goldring

Bérenbaum

2015

Current Opinion in Pharmacology

150

124

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“…Pharmacological manipulation of this pathway is feasible with the use of PPARγ agonists, such as rosiglitazone and pioglitazone. Indeed, pioglitazone inhibits TLR4-mediated pro-inflammatory effects of AGEs, including the induction of cyclooxygenase (COX)-2, HMGB1, interleukin (IL)-6 and MMP-13 (53). While prostaglandin E2 (PGE2) is a key pro-inflammatory mediator in OA pathogenesis (54), PGD2 counteracts PGE2-dependent induction of TLR4 and its downstream functions, including nuclear factorkappaB (NF-κB) activation in chondrocytes (55).…”

Section: Innate Immune Inhibitors In Oamentioning

confidence: 99%

“…Mice with cartilage-specific deletion of PPARγ show increased cartilage catabolism and synovial inflammation developing an OA-phenotype (53). Advanced glycation end products (AGE)-induced downregulation of PPARγ is dependent on TLR4 in chondrocytes (52).…”

Section: Innate Immune Inhibitors In Oamentioning

confidence: 99%

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An update on the up and coming therapies to treat osteoarthritis, a multifaceted disease

Roman‐Blas

Bizzi

Largo

et al. 2016

Expert Opinion on Pharmacotherapy

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Despite the renewed interest in the search of new compounds for treatment of OA, results have been limited. Novel systemic and IA administered agents are in active development. IA drug administration is particularly an attractive approach because can diminish some of the severe side effects associated with systemic drugs. Indeed, one of the most promising fields for pharmacology innovation in OA is joint injected therapy, as suggested by preliminary data from recent studies using IA sprifermin (rhFGF-18), mesenchymal stem cells or TGF-B1 transduced allogenic chondrocytes. Last, the effort to develop new drugs must be accompanied by the interest for establishing well-defined phenotypes, and only then, a more tailored therapy should be practiced in OA.

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“…Interestingly, PPARγ is also an important regulator of cell autophagy, likely through its influence on mTOR signaling. The specific deletion of PPARγ in cartilage results in disturbed endochondral bone development [33] as well as spontaneous OA [34]. These PPARγ-deficient mice also display accelerated cartilage breakdown following DMM surgery, due to reduced autophagy and increased cartilage catabolism [35•].…”

Section: Autophagy In Cartilage Homeostasismentioning

confidence: 99%

Novel Insights into Osteoarthritis Joint Pathology from Studies in Mice

Moon

Beier

2015

Curr Rheumatol Rep

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Osteoarthritis causes tremendous individual suffering and staggering societal costs, but due to our limited understanding of the underlying molecular and cellular mechanisms, our avenues for treating this disease are very restricted. Recent years have seen a drastic increase in the use of genetically modified mice to characterize the pathophysiology of osteoarthritis. Many new players and mechanisms driving osteoarthritis pathogenesis have been elucidated, some of which might be strong candidates as therapeutic targets for the human disease. The current review summarizes key findings (selected subjectively by the authors) from mouse osteoarthritis studies over recent years.

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Adult Cartilage-Specific Peroxisome Proliferator–Activated Receptor Gamma Knockout Mice Exhibit the Spontaneous Osteoarthritis Phenotype

Cited by 67 publications

References 36 publications

Emerging targets in osteoarthritis therapy

Emerging targets in osteoarthritis therapy

An update on the up and coming therapies to treat osteoarthritis, a multifaceted disease

Novel Insights into Osteoarthritis Joint Pathology from Studies in Mice

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