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Therapeutics in Osteoarthritis Based on an Understanding of Its Molecular Pathogenesis.

ABSTRACT: Osteoarthritis (OA) is the most prevalent joint disease in older people and is characterized by the progressive destruction of articular cartilage, synovial inflammation, changes in subchondral bone and peri-articular muscle, and pain. Because our understanding of the aetiopathogenesis of OA remains incomplete, we haven't discovered a cure for OA yet. This review appraises novel therapeutics based on recent progress in our understanding of the molecular pathogenesis of OA, including pro-inflammatory and pro-catabolic mediators and the relevant signalling mechanisms. The changes in subchondral bone and peri-articular muscle accompanying cartilage damage are also reviewed.

SUBMITTER: Kim JR

PROVIDER: S-EPMC5877535 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Therapeutics in Osteoarthritis Based on an Understanding of Its Molecular Pathogenesis.

Kim Ju-Ryoung JR Yoo Jong Jin JJ Kim Hyun Ah HA

International journal of molecular sciences 20180227 3

Osteoarthritis (OA) is the most prevalent joint disease in older people and is characterized by the progressive destruction of articular cartilage, synovial inflammation, changes in subchondral bone and peri-articular muscle, and pain. Because our understanding of the aetiopathogenesis of OA remains incomplete, we haven't discovered a cure for OA yet. This review appraises novel therapeutics based on recent progress in our understanding of the molecular pathogenesis of OA, including pro-inflamma ...[more]

PMID: 29495538

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Project description:BackgroundEwing sarcoma/PNET is managed with treatment paradigms involving combinations of chemotherapy, surgery, and sometimes radiation. Although the 5-year survival rate of non-metastatic disease approaches 70%, those cases that are metastatic and those that recur have 5-year survival rates of less than 20%. Molecularly targeted treatments offer the potential to further improve treatment outcomes.MethodsA PUBMED search was performed from 1997 to 2011. Published literature that included the topic of the Ewing sarcoma/PNET was also referenced.ResultsInsulin-like growth factor-1 receptor (IGF-1R) antagonists have demonstrated modest single agent efficacy in phase I/II clinical trials in Ewing sarcoma/PNET, but have a strong preclinical rationale. Based on in vitro and animal data, treatment using antisense RNA and cDNA oligonucleotides directed at silencing the EWS-FLI chimera that occurs in most Ewing sarcoma/PNET may have potential therapeutic importance. However drug delivery and degradation problems may limit this therapeutic approach. Protein-protein interactions can be targeted by inhibition of RNA helicase A, which binds to EWS/FLI as part of the transcriptional complex. Tumour necrosis factor related apoptosis inducing ligand induction using interferon has been used in preclinical models. Interferons may be incorporated into future chemotherapeutic treatment paradigms. Histone deacetylase inhibitors can restore TGF-β receptor II allowing TFF-β signalling, which appears to inhibit growth of Ewing sarcoma/PNET cell lines in vitro. Immunotherapy using allogeneic natural killer cells has activity in Ewing sarcoma/PNET cell lines and xenograft models. Finally, cyclin dependent kinase inhibitors such as flavopiridol may be clinically efficacious in relapsed Ewing sarcoma/PNET.ConclusionPreclinical evidence exists that targeted therapeutics may be efficacious in the ESFT. IGF-1R antagonists have demonstrated efficacy in phase I/II clinical trials, although predicting responses remains a challenge. The future treatment of Ewing sarcoma/PNET is likely to be improved by these scientific advances.

Dataset Information

Therapeutics in Osteoarthritis Based on an Understanding of Its Molecular Pathogenesis.

Publications

Therapeutics in Osteoarthritis Based on an Understanding of Its Molecular Pathogenesis.

Similar Datasets

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