Is osteoarthritis a metabolic disorder?

Kluzek, Stefan; Newton, John; Arden, N K

doi:10.1093/bmb/ldv028

Cited by 88 publications

(77 citation statements)

References 114 publications

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“…Obesity is one of the major risk factors for the development of osteoarthritis (OA) (1); however, the mechanisms involved are not clearly understood. Obesity is associated with elevated levels of free fatty acids (FFA) (2), resulting in lipid accumulation in non-adipose tissues.…”

Section: Introductionmentioning

confidence: 99%

Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells

Haywood

Yammani

2016

Osteoarthritis and Cartilage

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Introduction Obesity is the major risk factor for the development of osteoarthritis (OA); however, the mechanisms involved are not clearly understood. Obesity is associated with increased production of adipokine and elevated levels of circulating free fatty acids (FFA). A recent study has shown that saturated fatty acid palmitate induced pro-inflammatory and pro-apoptotic pathways in chondrocytes. Meniscus has been shown to be more susceptible than articular cartilage to catabolic stimuli. Thus, the aim of this study was to determine the effect of FFA (specifically, palmitate) on meniscus cells. Methods Cultured primary porcine meniscus cells were stimulated with 500 μM free fatty acids (palmitate and oleate) for 24 hours to induce endoplasmic reticulum (ER) stress. After treatment, cell lysates were prepared and immunoblotted for C/EBP homologous protein (CHOP). To determine the activation of unfolded protein response (UPR) signaling, cell lysates were probed for cJun n-terminal kinase (JNK), cleaved caspase -3 and Xbp-1s, an alternative mRNA splicing product generated due to Ire1α activation. Results Treatment of isolated primary meniscus cells with palmitate but not oleate induced expression of CHOP and Xbp-1s. Palmitate treatment of meniscus cells also activated JNK and increased expression of caspase-3, thus promoting apoptosis in meniscus cells. Conclusions Palmitate induces ER stress and promotes apoptotic pathways in meniscus cells. This is the first study to establish ER stress as a key metabolic mechanistic link between obesity and OA, in addition to (or operating with) biomechanical factors.

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Section: Introductionmentioning

confidence: 99%

Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells

Haywood

Yammani

2016

Osteoarthritis and Cartilage

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“…Compared with individuals with no OA, participants with total joint replacements have a 26% increased risk of CVD 14. Furthermore, a younger middle-aged population with OA have a fivefold increased prevalence of metabolic syndrome 15 16…”

Section: Introductionmentioning

confidence: 99%

Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women

et al. 2015

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“…We agree that it is plausible that painful KOA is an early sign of metabolic dysregulation, leading to CVD problems12 and this will be a focus of future research.…”

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confidence: 78%

Response to: ‘Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women’ by Gao et al

et al. 2016

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Response to: 'Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women' by Gao et alWe thank Gao et al 1 for their interest in our paper. 2Gao et al highlighted a number of issues related to discordance between pain and radiographic changes and sensitivity of the pain assessment. Although a single definition of knee osteoarthritis (KOA) remains elusive, the presence of knee pain is the main symptom of KOA 3-5 and there is still a strong relationship between pain and radiographic knee osteoarthritis (ROA).

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Is osteoarthritis a metabolic disorder?

Abstract: In an era of an obesity epidemic, this review identifies a need for well-designed cohort studies assessing early metabolic changes in populations at high risk of OA and MetS, and to identify risk factors for increased mortality in patients with OA.

Cited by 88 publications

References 114 publications

Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells

Free fatty acid palmitate activates unfolded protein response pathway and promotes apoptosis in meniscus cells

Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women

Response to: ‘Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women’ by Gao et al

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