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Osteoarthritis, a disease bridging development and regeneration.

ABSTRACT: The osteoarthritic diseases are common disorders characterized by progressive destruction of the articular cartilage in the joints, and associated with remodeling of the subchondral bone, synovitis and the formation of bone outgrowths at the joint margins, osteophytes. From the clinical perspective, osteoarthritis leads to joint pain and loss of function. Osteoarthritis is the leading cause of progressive disability. New data from genetic, translational and basic research have demonstrated that pathways with essential roles in joint and bone development also contribute to the postnatal homeostasis of the articular cartilage and are involved in osteoarthritis, making these potential therapeutic targets. Other systems of interest are the tissue-destructive enzymes that break down the extracellular matrix of the cartilage as well as mediators of inflammation that contribute to synovitis. However, the perspective of a durable treatment over years to decades highlights the need for a personalized medicine approach encompassing a global view on the disease and its management, thereby including nonpharmaceutical approaches such as physiotherapy and advanced surgical methods. Integration of novel strategies based on their efficacy and safety with the identification of individuals at risk and optimal individual rehabilitation management remains a major challenge for the medical community in particular, as the incidence of osteoarthritis is likely to further increase with the overall aging of the population.

SUBMITTER: Lories RJ

PROVIDER: S-EPMC3727791 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Project description:Osteoarthritis (OA) is a painful and disabling disease that affects millions of people worldwide. Symptom-alleviating treatments exist, although none with long-term efficacy. Furthermore, there are currently no disease-modifying OA drugs (DMOADs) with demonstrated efficacy in OA patients, which is, in part, attributed to a lack of full understanding of the pathogenesis of OA. The inability to translate findings from basic research to clinical applications also highlights the deficiencies in the available OA models at simulating the clinically relevant pathologies and responses to treatments in humans. In this review, the current status in the development of DMOADs will be first presented, with special attention to those in Phase II-IV clinical trials. Next, current in vitro, ex vivo, and in vivo OA models are summarized and the respective advantages and disadvantages of each are highlighted. Of note, the development and application of microphysiological or tissue-on-a-chip systems for modeling OA in humans are presented and the issues that need to be addressed in the future are discussed. Microphysiological systems should be given serious consideration for their inclusion in the DMOAD development pipeline, both for their ability to predict drug safety and efficacy in human clinical trials at present, as well as for their potential to serve as a test platform for personalized medicine. Impact statement At present, no disease-modifying osteoarthritis (OA) drugs (DMOADs) have been approved for widespread clinical use by regulatory bodies. The failure of developing effective DMOADs is likely owing to multiple factors, not the least of which are the intrinsic differences between the intact human knee joint and the preclinical models. This work summarizes the current OA models for the development of DMOADs, discusses the advantages/disadvantages of each, and then proposes future model development to aid in the discovery of effective and personalized DMOADs. The review also highlights the microphysiological systems, which are emerging as a new platform for drug development.

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Osteoarthritis, a disease bridging development and regeneration.

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