Cartilage regeneration and ageing: Targeting cellular plasticity in osteoarthritis

Varela‐Eirin, Marta; Loureiro, Jesús; Fonseca, Eduardo; Corrochano, Silvia; Caeiro, José Ramón; Collado, Manuel; Mayán, M.D.

doi:10.1016/j.arr.2017.12.006

Cited by 155 publications

(104 citation statements)

References 215 publications

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“…TGF-β can regulate multiple types of immune cells including T cells, B cells, macrophage, dendritic cells and natural killer cells 40. Additionally, TGF-β signalling is highly activated during tissue repair processes such as OA 41 42. Thus, the highly activated TGF-β signalling found in the OA+METS+/MLI+ group might represent elevated low-grade inflammation and the highly activated tissue repair processes.…”

Section: Discussionmentioning

confidence: 99%

Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice

Huang

Chen

et al. 2020

Ann Rheum Dis

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ObjectivesEmerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one ‘hit’ is provided by an adverse gut microbiome that activates innate immunity; the other ‘hit’ is underlying joint damage.MethodsMedical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability.ResultsHistological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1β, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations.ConclusionThe study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.

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Section: Discussionmentioning

confidence: 99%

Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice

Huang

Chen

et al. 2020

Ann Rheum Dis

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“…OA can be classified into two main types based on etiology: the natural occurring OA and the secondary OA. The natural occurring OA, or primary OA, is diagnosed in the absence of any predisposing event, but is associated with risk factors, especially age (Varela-Eirin et al, 2018). The secondary OA is associated with certain inducing factors, especially trauma (Kuyinu et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Comparison of early-stage changes of osteoarthritis in cartilage and subchondral bone between two different rat models

Yang

2020

PeerJ

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Osteoarthritis (OA) is a chronic degenerative joint disease and the major cause of joint pain and disability in the elderly. It is mainly characterized by articular cartilage degradation and subchondral bone remodeling. There are two main types of OA: natural occurring OA and secondary OA, mainly associated with aging and trauma, respectively. In this study, we established two OA models in rat knee joints to simulate the two types of OA, using the type II collagenase injection (CI) and anterior cruciate ligament transection (ACLT), respectively. After intervention for 2–6 weeks, cartilage and subchondral bone changes were detected in histological staining, immunochemistry, and micro-CT. Results showed that both models with typical pathology changes of OA were successfully induced, while the development and severity of OA process in the models were different. In ACLT rats, the cartilage damage was milder, lasted for a shorter time, and subchondral bone reconstruction occurred earlier, compared with the changes in CI rats. The cartilage damage was secondary to subchondral bone change in ACLT rats, while subchondral bone change was secondary to cartilage degeneration in CI rats. In conclusion, the interaction between cartilage and subchondral bone is different between the natural-occurring and secondary OA models. These two models not only suggest potential different mechanisms of the two types of OA, but also provide new directions for OA treatment and prevention.

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“…Osteoarthritis Osteoarthritis (OA) is a prevalent joint chronic disease, which is characterized by cartilage degeneration, including fibrosis of synovial membrane, synovial inflammation, and subchondral bone reconstruction, resulting in structural changes and function loss in articular cartilage of the hip, knee, and hand [55]. GWAS research revealed epigenetics altered OA-related gene expression without changing the DNA sequence, including DNA methylation, histone acetylation, and ncRNAs [56].…”

Section: Dna Methylation Of Ncrnas In Common Bone Diseasesmentioning

confidence: 99%

DNA methylation of noncoding RNAs: new insights into osteogenesis and common bone diseases

Xia

Cen

et al. 2020

Stem Cell Res Ther

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Bone diseases such as osteoarthritis, osteoporosis, and bone tumor present a severe public health problem. Osteogenic differentiation is a complex process associated with the differentiation of different cells, which could regulate transcription factors, cytokines, many signaling pathways, noncoding RNAs (ncRNAs), and epigenetic modulation. DNA methylation is a kind of stable epigenetic alterations in CpG islands without DNA sequence changes and is involved in cancer and other diseases, including bone development and homeostasis. ncRNAs can perform their crucial biological functions at the RNA level, and many findings have demonstrated essential functions of ncRNAs in osteogenic differentiation. In this review, we highlight current researches in DNA methylation of two relevant ncRNAs, including microRNAs and long noncoding RNAs, in the initiation and progression of osteogenesis and bone diseases.

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Cartilage regeneration and ageing: Targeting cellular plasticity in osteoarthritis

Cited by 155 publications

References 215 publications

Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice

Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice

Comparison of early-stage changes of osteoarthritis in cartilage and subchondral bone between two different rat models

DNA methylation of noncoding RNAs: new insights into osteogenesis and common bone diseases

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