Knee and hip articular cartilage have distinct epigenomic landscapes: implications for future cartilage regeneration approaches

Hollander, Wouter den; Ramos, Yolande F M; Bos, Steffan D.; Bömer, Nils; Breggen, Ruud van der; Lakenberg, Nico; Dijcker, Wesley J. de; Duijnisveld, B.J.; Slagboom, P. Eline; Nelissen, Rob G H H; Meulenbelt, Ingrid

doi:10.1136/annrheumdis-2014-205980

Cited by 103 publications

(96 citation statements)

References 23 publications

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“…This can be explained by the differences in cellular identity between the chondrocytes residing in either knee or hip articular cartilage [22]. Elevated MMP-12 has been found to increase cartilage degradation and play a role in inflammatory joint disease [23,24], be efficient at cleaving within both the intraglobular domain and the C-terminus of aggrecan in bovine articular cartilage [25] and be regulated by hypoxia-inducible factor 1a during cartilage destruction in OA [26].…”

Section: Discussionmentioning

confidence: 99%

Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity

et al. 2015

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“…Of these modifications, DNA methylation is the most extensively characterized in OA [5–10]. Although sometimes associated with gene activation, methylation of clustered CpG dinucleotides within a gene promoter is most often correlated with gene repression [11].…”

Section: Introductionmentioning

confidence: 99%

Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis

Bradley

Carpio

McGee‐Lawrence

et al. 2016

Osteoarthritis and Cartilage

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OBJECTIVE Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. OA is characterized by articular chondrocyte deterioration, subchondral bone changes and debilitating pain. One strategy to promote cartilage regeneration and repair is to accelerate proliferation and matrix production of articular chondrocytes. We previously reported that the protein phosphatase Phlpp1 controls chondrocyte differentiation by regulating the activities of anabolic kinases. Here we examined the role of Phlpp1 in osteoarthritis progression in a murine model. We also assessed PHLPP1 expression and promoter methylation. DESIGN Knee joints of WT and Phlpp1−/− mice were surgically destabilized by transection of the medial meniscal ligament (DMM). Mice were assessed for signs of OA progression via radiographic and histological analyses, and pain assessment for mechanical hypersensitivity using the von Frey assay. Methylation of the PHLPP1 promoter and PHLPP1 expression was evaluated in human articular cartilage and chondrocyte cell lines. RESULTS Following DMM surgeries, Phlpp1 deficient mice showed fewer signs of OA and cartilage degeneration. Mechanical allodynia associated with DMM surgeries was also attenuated in Phlpp1−/− mice. PHLPP1 was highly expressed in human articular cartilage from OA patients, but was undetectable in cartilage specimens from femoral neck fractures. Higher PHLPP1 levels correlated with less PHLPP1 promoter CpG methylation in cartilage from OA patients. Blocking cytosine methylation or treatment with inflammatory mediators enhanced PHLPP1 expression in human chondrocyte cell lines. CONCLUSION Phlpp1 deficiency protects against OA progression while CpG demethylation and inflammatory responses promote PHLPP1 expression.

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“…Radiographic knee osteoarthritis was associated with several singlenucleotide polymorphisms (SNPs), including LRP5 [21] and severe hand osteoarthritis was associated with variants within the aldehyde dehydrogenase (ALDH1A2) gene, involved in the vitamin A metabolism [22]. Hip and knee osteoarthritis are also associated with epigenetic mechanisms [23]. Differentially methylated regions, associated with cell differentiation and skeletal embryogenesis, were found in subchondral trabecular bone in the femoral head of patients with osteoporosis and osteoarthritis [24].…”

Section: Genetic and Epigenetic Background In Osteoporosis And Osteoamentioning

confidence: 98%

Osteoporosis and osteoarthritis

Geusens¹,

Bergh

2016

Current Opinion in Rheumatology

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Knee and hip articular cartilage have distinct epigenomic landscapes: implications for future cartilage regeneration approaches

Cited by 103 publications

References 23 publications

Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity

Macrophage-specific metalloelastase (MMP-12) immunoexpression in the osteochondral unit in osteoarthritis correlates with BMI and disease severity

Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis

Osteoporosis and osteoarthritis

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