Modern-day environmental factors in the pathogenesis of osteoarthritis

Bérenbaum, Francis; Wallace, Ian J.; Lieberman, Daniel E.; Felson, David T.

doi:10.1038/s41584-018-0073-x

Cited by 211 publications

(177 citation statements)

References 108 publications

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“…However, the metabolic alterations that define the MS are considered among the four major environmental factors that are associated with the OA pathogenesis (27). In addition, (i) studies on painful interphalangeal OA showed that MS is significantly associated with the disease, even adjusting for both age and BMI (28) and (ii) a follow-up study carried out on a high number of subjects suggests that both overweight and obesity increase the risk of incidenthand OA, a joint not subjected to mechanical overload (7).…”

Section: Discussionmentioning

confidence: 99%

Oleate prevents palmitate-induced mitochondrial dysfunction in chondrocytes

Vaquez-Mosquera

Fernández-Moreno

Cortés-Pereira

et al. 2020

Preprint

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BACKGROUND : The clear association between obesity and osteoarthritis (OA) in joints not subjected to mechanical overload, together with the relationship between OA and metabolic syndrome (MS), suggests that there are systemic factors related to metabolic disorders that are involved in the metabolic phenotype of OA. The aim of this work is to study the effects of palmitate (PA) and oleate (OL), as the most abundant fatty acids (FA) present in the diet and serum, on cellular metabolism in an " in vitro " model of human chondrocytes. METHODS :.The Seahorse XF96 Analyzer was used tomeasure the mitochondrial, glycolytic function and the contribution of the mitochondrial oxidative phosphorilation system (OXPHOS) and glycolysis to the production of ATP, in the T/C-28a2 chondrocyte treated with to PA, OL and palmitate/oleate (PA/OL) ratio 1:2. Subsequently ATP bioluminescence assay kit was used for ATP quantification. To detect the presence of lipid droplets, two types of stains were performed and the amount of Triglycerides was quantified spectrophotometrically. RESULTS : PA, but not OL, produces mitochondrial dysfunction observed with a lower rate of OCR intended for the synthesis of ATP, coupling efficiency, maximal respiration and spare respiratory capacity. Glycolytic function showed lower rates for both glycolytic capacity and glycolytic reserve when cells were incubated withFA in relation to basal condition (BC). The production rate of ATP from OXPHOS showed lower values in chondrocytes incubated with any of the FAs. The evaluation of possible formation of Lipid droplets (LD) showed a significant increase of these structures in FA conditions, being significantly higher when the cells were incubated with OL. CONCLUSIONS : PA and OL show antagonistic effects in human chondrocytes; while increased levels of PA induce mitochondrial dysfunction and hinder the response of chondrocytes through the glycolytic pathway, OL shows a cytoprotective effect through which promotes the formation of triglycerides-rich LD, as well as the incorporation of PA.

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Section: Discussionmentioning

confidence: 99%

Oleate prevents palmitate-induced mitochondrial dysfunction in chondrocytes

Vaquez-Mosquera

Fernández-Moreno

Cortés-Pereira

et al. 2020

Preprint

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“…21 Chondrocyte apoptosis is generally considered a vital pathological feature of OA. 21 Chondrocyte apoptosis is generally considered a vital pathological feature of OA.…”

Section: Discussionmentioning

confidence: 99%

“…Osteoarthritis is caused by various factors, such as biomechanical forces, metabolic distress, cytokine occurrence, genetic heritage, cartilage condition, chondrocyte apoptosis and free radical generation. 21 Chondrocyte apoptosis is generally considered a vital pathological feature of OA. Weakening the course of chondrocyte apoptosis can ameliorate the progress of joint cartilage degeneration.…”

Section: Discussionmentioning

confidence: 99%

Ligustilide attenuates nitric oxide‐induced apoptosis in rat chondrocytes and cartilage degradation via inhibiting JNK and p38 MAPK pathways

Zhou

Jiang

et al. 2019

J Cellular Molecular Medi

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Ligustilide ( LIG ) is the main lipophilic component of the Umbelliferae family of pharmaceutical plants, including Radix angelicae sinensis and Ligusticum chuanxiong. LIG shows various pharmacological properties associated with anti‐inflammation and anti‐apoptosis in several kinds of cell lines. However, the therapeutic effects of LIG on chondrocyte apoptosis remain unknown. In this study, we investigated whether LIG had an anti‐apoptotic activity in sodium nitroprusside ( SNP )‐stimulated chondrocyte apoptosis and could delay cartilage degeneration in a surgically induced rat OA model, and elucidated the potential mechanisms. In vitro studies revealed that LIG significantly suppressed chondrocyte apoptosis and cytoskeletal remodelling, which maintained the nuclear morphology and increased the mitochondrial membrane potential. In terms of SNP , LIG treatment considerably reduced the expression levels of cleaved caspase‐3, Bax and inducible nitric oxide synthase and increased the expression level of Bcl‐2 in a dose‐dependent manner. The LIG ‐treated groups presented a significantly suppressed expression of activating transcription factor 2 and phosphorylation of Jun N‐terminal kinase ( JNK ) and p38 mitogen‐activated protein kinase ( MAPK ). The inhibitory effect of LIG was enhanced by the p38 MAPK inhibitor SB 203580 or the JNK inhibitor SP 600125 and offset by the agonist anisomycin. In vivo studies demonstrated that LIG attenuated osteoarthritic cartilage destruction by inhibiting the cartilage chondrocyte apoptosis and suppressing the phosphorylation levels of activating transcription factor 2, JNK and p38 MAPK . This result was confirmed by histological analyses, micro‐ CT , TUNEL assay and immunohistochemical analyses. Collectively, our studies indicated that LIG protected chondrocytes against SNP ‐induced apoptosis and delayed articular cartilage degeneration by suppressing JNK and p38 MAPK pathways.

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“…Felson in Nature Review Rheumatology entitled: "Modern-day environmental factors in the pathogenesis of osteoarthritis" has challenged our understanding of the pathogenesis of osteoarthritis (OA). n this original and timely article the authors propose the possibility that osteoarthritis (OA) is an evolutionary mismatch disease 1 . They argue that OA is much more common today than in the past because deleterious genes inherited from previous generations may be inadequately or imperfectly adapted to our modern environment.…”

Section: Commentarymentioning

confidence: 99%

Osteoarthritis (OA): A Modern Disease of the Anthropocene Era

Mobasheri

Levesque

2019

Preprint

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In this paper we discuss recent studies that have unravelled important roles for modern-day environmental factors in the pathogenesis of osteoarthritis (OA). OA is a relatively modern disease in terms of human evolution. While our ancestors have been around for about six million years, modern humans (Homo sapiens) only evolved about 200,000 years ago. Early humans did not live long enough to suffer from age-related musculoskeletal conditions such as OA and arthritic diseases are thought to have been extremely rare in early Natufians and Egyptians, but this is probably because of an underrepresentation of older adults in the skeletal records. Examination of Egyptian skeletal records from burial sites provides some evidence of arthritic diseases such as OA, but mainly in the mummified remains of pharaohs and high-ranking officials, viziers, priests and nobles. Examination of the skeletal records in Roman burial ground does reveal more evidence of arthritic diseases but the evidence is sketchy and we can only assume that arthritic diseases were more prevalent in the slave population in ancient Egypt and the Roman Empire. Recent studies indicate that independent risk factors for knee OA either arose or have become amplified in the post-industrial era, suggesting that the prevalence of OA has gradually increased since the industrial revolution. Alarmingly, the incidence of knee OA has doubled since the middle of the 20thcentury, suggesting that OA is a modern disease of the Anthropocene era and there may be unknown environmental factors that have led to its increased incidence since industrialization.

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Modern-day environmental factors in the pathogenesis of osteoarthritis

Cited by 211 publications

References 108 publications

Oleate prevents palmitate-induced mitochondrial dysfunction in chondrocytes

Oleate prevents palmitate-induced mitochondrial dysfunction in chondrocytes

Ligustilide attenuates nitric oxide‐induced apoptosis in rat chondrocytes and cartilage degradation via inhibiting JNK and p38 MAPK pathways

Osteoarthritis (OA): A Modern Disease of the Anthropocene Era

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