Osteoarthritis phenotypes and novel therapeutic targets

Spil, W.E. van; Kubassova, Olga; Boesen, Mikael; Bay‐Jensen, Anne‐Christine; Mobasheri, Ali

doi:10.1016/j.bcp.2019.02.037

Cited by 169 publications

(146 citation statements)

References 55 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…Osteoarthritis (OA) is a degenerative joint disease that commonly occurs in the elderly. It is reported that around 15% of the population suffer from OA in the world . Based on the results from epidemiological survey in China, about 4% of Chinese population is diagnosed with OA.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

LncRNA PART‐1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR‐590‐3p sponge in osteoarthritis

Lü

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Osteoarthritis (OA) is a degenerative joint disease that commonly occurs in the elderly. This study focused on apoptosis and explored the modulating effects of long non‐coding (lncRNAs) prostate androgen‐regulated transcript‐1 (PART‐1) on chondrocytes apoptosis. In the present study, the PART‐1 expression level was down‐regulated in the OA cartilages. Silence of PART‐1 decreased the cell viability and promoted chondrocytes apoptosis. Overexpression of PART‐1 could reverse the effects induced by interleukin 1β (IL‐1β) stimulation, thus slowing down the apoptosis rate. MiR‐590‐3p was found to be the potential target, and RNA immunoprecipitation and luciferase activity assay confirmed the binding between PART‐1 and miR‐590‐3p. Moreover, miR‐590‐3p was down‐regulated by PART‐1 and was negatively associated with PART‐1. Transforming growth factor‐beta receptor type 2 (TGFBR2) was positively associated with PART‐1. Down‐regulation of PART‐1 decreased cell viability and induced cell apoptosis, which was partially reversed by miR‐590‐3p silence or TGFBR2 overexpression; while overexpression of PART‐1 increased the cell viability and decreased the caspase 3 activity and apoptotic rates, and the effects were partially attenuated by miR‐590‐3p overexpression or silence of TGFBR2 in IL‐1β‐stimulated chondrocytes. Knock‐down of PART‐1 down‐regulated both Smad3 and p‐Smad3 protein levels, which was reversed by miR‐590‐3p inhibition or TGFBR2 overexpression. Smad3 expression level was lower in the OA group than that in the normal group and was positively associated with the PART‐1 expression level. Collectively, the study revealed that lncRNA PART‐1 regulates the apoptosis of chondrocytes in OA by acting as a sponge for miR‐590‐3p, which subsequently regulates TGFBR2/Smad3 signalling.

show abstract

Section: Introductionmentioning

confidence: 99%

“…It is reported that around 15% of the population suffer from OA in the world. 1,2 Based on the results from epidemiological survey in China, about 4% of Chinese population is diagnosed with OA. For the people over 60 years old, the incidence of OA reaches as high as 42.8%.…”

Section: Introductionmentioning

confidence: 99%

LncRNA PART‐1 targets TGFBR2/Smad3 to regulate cell viability and apoptosis of chondrocytes via acting as miR‐590‐3p sponge in osteoarthritis

Lü

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…A number of strati cations have been proposed on the basis of speci c pathological processes to classify different mechanistic subgroups, which include an increased in ammatory component, mechanical overload, metabolic alterations, and cell senescence [37]. Knowledge of the heterogeneity of OA would help better de ne potential treatment targets, improve the ability to select appropriate patients for future clinical interventions and adapt outcome measures to the situation [38]. To identify potential subgroups based on their expression pro les, we performed KNN clustering.…”

Section: Identi Cation and Characterization Of Molecular Subgroupsmentioning

confidence: 99%

Identification of Key Regulators Responsible for Dysregulated Networks in Osteoarthritis by Large-Scale Expression Analysis

Song

Wan

Zhou

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Osteoarthritis (OA) is a worldwide musculoskeletal disorder. However, disease-modifying therapies for OA are not available. Here, we aimed to characterize the molecular signatures of OA and to identify novel therapeutic targets and strategies to improve the treatment of OA.Methods: We collected genome-wide transcriptome data performed on 161 OA and 88 normal human cartilage or synovium tissues from 9 independent datasets. Differential gene expression analysis and functional enrichment were performed to identify genes and pathways that were dysregulated in OA. The computational drug repurposing method was used to uncover drugs that could be repurposed to treat OA.Results: We identified several pathways associated with the development of OA, such as extracellular matrix adhesion, inflammation, carbohydrate metabolism, and collagen organization. By protein-protein interaction (PPI) network analysis, we prioritized several hub genes, such as JUN, IL-6, VAMP8, and SOCS3. Moreover, we repurposed several FDA-approved drugs, such as cardiac glycosides, that could be used in the treatment of OA. Conclusions: We proposed that the hub genes we identified will play a role in cartilage homeostasis and could be important diagnostic and therapeutic targets. Drugs such as protein kinase inhibitors and cardiac glycosides could improve the treatment of OA.

show abstract

“…Conjecturally, up to 240 million people around the world suffer from OA. The observed symptoms (e.g., pain, stiffness, joint instability, and pain-related psychological distress) start approximately at the age of 55 and have devastating consequences in the quality of life of the patients (Hunter et al, 2008;Van Spil et al, 2019). In 2013, OA was the second most expensive health condition treated at US hospitals with $16.5 billion expenditure (Torio and Moore, 2013).…”

Section: Introductionmentioning

confidence: 99%