Current concepts in the pathogenesis of osteoarthritis

Krasnokutsky, Svetlana; Attur, Mukundan; Palmer, Glyn D.; Samuels, Jonathan; Abramson, Steven B.

doi:10.1016/j.joca.2008.06.025

Cited by 176 publications

(171 citation statements)

References 14 publications

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“…type II collagen) or from an idiopathic etiology. In any case, OA arises when an irreversible imbalance occurs between the synthesis and degradation of the ECM, resulting in a number of molecular changes in chondrocyte phenotype and gene expression [6][7][8] (Figure 2). …”

Section: Etiology and Pathophysiology Of Oamentioning

confidence: 99%

Modulating hedgehog signaling can attenuate the severity of osteoarthritis

Lin

Seeto

Bartoszko

et al. 2009

Nat Med

286

340

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Osteoarthritis is associated with the irreversible degeneration of articular cartilage. Notably, in this condition, articular cartilage chondrocytes undergo phenotypic and gene expression changes that are reminiscent of their end-stage differentiation in the growth plate during skeletal development. Hedgehog (Hh) signaling regulates normal chondrocyte growth and differentiation; however, the role of Hh signaling in chondrocytes in osteoarthritis is unknown. Here I examined human osteoarthritic samples and mice in which osteoarthritis was surgically induced and find that Hh signaling is activated in osteoarthritis. Using several genetically modified mice, I found that higher levels of Hh signaling in chondrocytes cause a more severe osteoarthritic phenotype. Furthermore, Ishow in mice and in human cartilage explants that pharmacological or genetic inhibition of Hh signaling reduces the severity of osteoarthritis and that runtrelated transcription factor-2 (Runx2) potentially mediates this process by regulating a disintegrin and metalloproteinase with thrombospondin type 1 motif-5 (Adamts5) expression. Together, these findings raise the possibility that Hh blockade can be used as a therapeutic approach to inhibit articular cartilage degeneration.iii ACKNOWLEDGEMENTS

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Section: Etiology and Pathophysiology Of Oamentioning

confidence: 99%

Modulating hedgehog signaling can attenuate the severity of osteoarthritis

Lin

Seeto

Bartoszko

et al. 2009

Nat Med

286

340

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“…Moreover, OA is associated with an extremely high economic burden, which is largely attributable to the effects of disability and the expense of the treatments as well as the impaired quality of life [1]. The disease is characterized by a progressive loss of articular cartilage that causes chronic pain and compromises joint function.…”

mentioning

confidence: 99%

Effects of sesamin on the biosynthesis of chondroitin sulfate proteoglycans in human articular chondrocytes in primary culture

et al. 2013

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“…Pain associated with inflammation appears to be the most serious sign of OA [3,[11][12][13][14][15][16]30]. As stated in the introduction, pathophysiology of OA is very complex due to involvement of multiple factors [18,[20][21][22][23][24][25][26]. Among all these factors, oxidative stress (due to excess generation of free radicals) and inflammation are proven to be the major contributing factors in joint damage and pain [67][68][69][70][71].…”

Section: Discussionmentioning

confidence: 99%

“…Cells in damaged joints release cytokines (IL-1β and IL-6), tumor necrosis factor-α (TNF-α), followed by stimulation of mitogen activated protein kinase (MAPK), matrix metalloproteinases (MMP-1, MMP-3, and MMP-13), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), phospholipase 2A, nitric oxide (NO), prostaglandin E2 (PGE2), and platelet activating factor (PAF). These cascading events and many others cause inflammation, subchondral bone thickening, breakdown of proteoglycans and destruction of cartilage [19,[22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Terminalia chebula Extract for Anti-Arthritic Efficacy and Safety in Osteoarthritic Dogs

Murdock¹,

Vega³

et al. 2015

J Veterinar Sci Technol

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The present investigation was undertaken to assess anti-inflammatory and anti-arthritic efficacy and safety of T. chebula extract (TCE) in moderately osteoarthritic (OA) dogs. Dogs with OA received either 500 mg placebo or 500 mg TCE twice daily for 150 days. On a monthly basis, dogs were given a full physical exam and were evaluated for arthritic pain (overall pain, pain upon limb manipulation, and pain after physical exertion), inflammation (erythrocyte sedimentation rate, ESR), and analysis of complete blood count (CBC) and serum biomarkers of liver (bilirubin, ALT, and AST), kidney (BUN and creatinine), and heart and skeletal muscle (CK) functions. Elbow and stifle joints were radiographed on day 0 and day 150 for evaluation of arthritic progression. Dogs given TCE showed significant (P<0.01) reductions in overall pain, pain upon limb manipulation, and pain after physical exertion by day 90, with maximum effects on day 150 (81.2%, 81.5%, and 84.2%, respectively). A marked reduction in ESR coincided with pain reduction in TCE-treated dogs, which was indicative of anti-inflammatory effect of TCE. Radiographic evidence also indicated slowed progression of OA in joints examined. No significant change occurred in physical parameters, CBC parameters, or serum biomarkers in dogs on placebo or treatment, which suggested that TCE was well tolerated. It can be concluded that TCE, by having many active principles (chebulagic acid, chebulinic acid, corilagin, hydrolysable tannoids, etc.) might have provided antioxidant, anti-inflammatory and anti-arthritic effects in dogs without causing any side effects.

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Current concepts in the pathogenesis of osteoarthritis

Cited by 176 publications

References 14 publications

Modulating hedgehog signaling can attenuate the severity of osteoarthritis

Modulating hedgehog signaling can attenuate the severity of osteoarthritis

Effects of sesamin on the biosynthesis of chondroitin sulfate proteoglycans in human articular chondrocytes in primary culture

Evaluation of Terminalia chebula Extract for Anti-Arthritic Efficacy and Safety in Osteoarthritic Dogs

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