Joint Injury in Young Adults and Risk for Subsequent Knee and Hip Osteoarthritis

Gelber, Allan C.; Hochberg, Marc C.; Mead, Lucy A.; Wang, Nae Yuh; Wigley, Fredrick M.; Klag, Michael J.

doi:10.7326/0003-4819-133-5-200009050-00007

Cited by 653 publications

(510 citation statements)

References 27 publications

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“…Alone, SHU9119 caused a modest inhibition of IL-1 but had no effect on TNF--induced IL-6 or IL-8 production, consistent with its dual agonist/antagonist nature. Remarkably, while SHU9119 was unable to block the effect of -MSH, it abridged the anti-inflammatory activity of D[TRP] 8 --MSH, thus suggesting a potential role for MC 3 in chondroprotection, which agrees with previous studies reporting MC 3 agonist activity of this peptide [51,76,79]. Moreover, at higher concentrations of -MSH, the presence of SHU9119 synergistically reduced IL-6 release, thereby signifying that SHU9119 may be concerting efforts with -MSH via either activation of MC 1 and/or MC 5 .…”

supporting

confidence: 91%

“…However, in spite of the potential of melanocortin peptides to limit inflammation, few studies have looked at their chondroprotective properties. We have recently demonstrated that both the melanocortin receptor pan-agonist -MSH and [DTRP 8 ]--MSH (structures shown in Table 1), which shows selectivity for MC 3 , ameliorate TNF--induced chondrocyte apoptosis and the release of pro-inflammatory cytokines and MMP's [64]. Now, we describe the ability of the of melanocortins to: 1) prompt a homeostatic control over impact-induced inflammatory cytokine production, 2) confine chondrocyte death and cartilage damage to injury site, whilst…”

Section: Discussionmentioning

confidence: 99%

“…Traumatic joint injuries are a major risk factor for the development and progression of OA [2] and increase the risk of arthritis 5 to 17-fold [3,4]. Knee traumas, in particular, represent over 40% of all sports injuries [5][6][7] and often result from traffic accidents with surgical restoration of joint stability not preventing future arthritis development [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Kaneva

Kerrigan

Grieco

et al. 2014

Biochemical Pharmacology

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Conclusion:Melanocortin peptide pre-treatment prevented chondrocyte death following mechanical impact to cartilage and led to a marked reduction of pro-inflammatory cytokines, whilst prompting the production of anti-inflammatory/pro-resolving cytokine IL-10.Development of small molecule agonists towards melanocortin receptors could thus be a viable approach for preventing chondrocyte inflammation and death within cartilage and represent an alternative approach for the treatment of osteoarthritis.

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supporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Kaneva

Kerrigan

Grieco

et al. 2014

Biochemical Pharmacology

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“…Recent estimates suggest that posttraumatic arthritis is responsible for 12% of the 21 million cases of OA in the US, at a cost of ϳ$7 billion annually to the US economy (2). Posttraumatic arthritis also causes disability in young and middle-aged patients, unlike idiopathic OA (3)(4)(5)(6).…”

mentioning

confidence: 99%

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

Ward¹,

Furman²,

Huebner³

et al. 2008

Arthritis & Rheumatism

112

127

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Objective. Posttraumatic arthritis is a frequent long-term complication of intraarticular fractures. A model of a closed intraarticular fracture in C57BL/6 mice that progresses to posttraumatic arthritis has been developed. The MRL/MpJ mouse has shown unique regenerative abilities in response to injury. The objective of this study was to determine if the MRL/MpJ mouse is protected from posttraumatic arthritis after intraarticular fractures.Methods. Intraarticular fractures were created in MRL/MpJ mice and C57BL/6 control mice (n ‫؍‬ 16 each). Limbs were analyzed for posttraumatic arthritis 4 and 8 weeks after fracture using microfocal computed tomography bone morphology, subchondral bone thickness evaluation, and histologic evaluation of cartilage degeneration. Serum cytokines and biomarkers were measured after the mice were killed.Results. Intraarticular fractures were successfully created in all 32 mice. In the experimental fractured limbs, C57BL/6 mice had a decrease in bone density, increased subchondral bone thickness, and increased cartilage degeneration compared with normal contralateral control limbs. In the MRL/MpJ mice, no differences in bone density, subchondral bone thickness, or histologic grading of cartilage degeneration were seen between fractured and contralateral control limbs. Cytokine analysis showed lower systemic levels of the proinflammatory cytokine interleukin-1␣ (IL-1␣) and higher levels of the antiinflammatory cytokines IL-4 and IL-10 in the MRL/MpJ mice.Conclusion. This study shows that the MRL/MpJ mouse is relatively protected from posttraumatic arthritis after intraarticular fracture. Further investigation into the mechanism involved in this response will hopefully provide new insight into the pathogenesis, prevention, and treatment of posttraumatic arthritis after intraarticular fracture.

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“…Acute traumatic joint injury in young adults leads to an increased risk of developing osteoarthritis (OA) later in life (1)(2)(3), despite efforts to intervene in this process by surgically stabilizing injured joints (4). Although the mechanism by which injury leads to tissue degeneration remains to be elucidated, several injuryrelated factors may contribute to the development of OA.…”

mentioning

confidence: 99%

Mechanical injury of cartilage explants causes specific time‐dependent changes in chondrocyte gene expression

Lee

Fitzgerald

DiMicco

et al. 2005

Arthritis & Rheumatism

198

172

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Objective. Joint injury in young adults leads to an increased risk of developing osteoarthritis (OA) later in life. This study was undertaken to determine if injurious mechanical compression of cartilage explants results in changes at the level of gene transcription that may lead to subsequent degradation of the cartilage.Methods. Cartilage was explanted from the femoropatellar groove of newborn calves. Levels of messenger RNA encoding matrix molecules, proteases, their natural inhibitors, transcription factors, and cytokines were assessed in free swelling control cultures as compared with cartilage cultures at 1, 2, 4, 6, 12, and 24 hours after application of a single injurious compression.Results. Gene-expression levels measured in noninjured, free swelling cartilage varied over 5 orders of magnitude. Matrix molecules were the most highly expressed of the genes tested, while cytokines, matrix metalloproteinases (MMPs), aggrecanases (ADAMTS-5), and transcription factors showed lower expression levels. Matrix molecules showed little change in expression after injurious compression, whereas MMP-3 increased ϳ250-fold, ADAMTS-5 increased ϳ40-fold, and tissue inhibitor of metalloproteinases 1 increased ϳ12-fold above the levels in free swelling cultures. Genes typically used as internal controls, GAPDH and ␤-actin, increased expression levels ϳ4-fold after injury, making them unsuitable for use as normalization genes in this study. The expression levels of tumor necrosis factor ␣ and interleukin-1␤, cytokines known to be involved in the progression of OA, did not change in the chondrocytes after injury. Conclusion.Changes in the level of gene expression after mechanical injury are gene specific and time dependent. The quantity of specific proteins may be altered as a result of these changes in gene expression, which may eventually lead to degradation at the tissue level and cause a compromise in cartilage structure and function.

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Joint Injury in Young Adults and Risk for Subsequent Knee and Hip Osteoarthritis

Abstract: Young adults with knee injuries are at considerably increased risk for osteoarthritis later in life and should be targeted in the primary prevention of osteoarthritis.

Cited by 653 publications

References 27 publications

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Melanocortin peptides protect chondrocytes from mechanically induced cartilage injury

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

Mechanical injury of cartilage explants causes specific time‐dependent changes in chondrocyte gene expression

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