Recent Insights into the Contribution of the Changing Hypertrophic Chondrocyte Phenotype in the Development and Progression of Osteoarthritis.

Ellen G J Ripmeester,Ufuk Tan Timur,Tim J M Welting,Marjolein M J Caron

doi:10.3389/fbioe.2018.00018

Ellen G J Ripmeester, Ufuk Tan Timur + Show 2 more

Open Access

https://doi.org/10.3389/fbioe.2018.00018

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Abstract

Osteoarthritis (OA) is an extremely prevalent age-related condition. The economic and societal burden due to the cost of symptomatic treatment, inability to work, joint replacement, and rehabilitation is huge and increasing. Currently, there are no effective medical therapies that delay or reverse the pathological manifestations of OA. Current treatment options are, without exception, focused on slowing down progression of the disease to postpone total joint replacement surgery for as long as possible and keeping the associated pain and joint immobility manageable. Alterations in the articular cartilage chondrocyte phenotype might be fundamental in the pathological mechanisms of OA development. In many ways, the changing chondrocyte phenotype in osteoarthritic cartilage resembles the process of endochondral ossification as seen, for instance, in developing growth plates. However, the relative contribution of endochondral ossification to the changing chondrocyte phenotype in the development and progression of OA remains poorly described. In this review, we will discuss the current knowledge regarding the cartilage endochondral phenotypic changes occurring during OA development and progression, as well as the molecular and environmental effectors driving these changes. Understanding how these molecular mechanisms determine the chondrocyte cell fate in OA will be essential in enabling cartilage regenerative approaches in future treatments of OA.

Highlights

Osteoarthritis (OA) is the most common degenerative joint disorder worldwide and its incidence rises with age (Loeser et al, 2012)
We noticed that the majority of the papers could be classified into signaling pathways known to be involved in endochondral ossification, such as Wnt, Ihh/PTHrP, TGF-β, MAP-kinases, fibroblast growth factor (FGF), Notch signaling, inflammatory signaling, and hypoxia-associated signaling pathways
Besides these pathways papers describing processes, such as angiogenesis and matrix mineralization were found. These pathways and processes involved in endochondral ossification will be described separately and new insights from the selected literature will be discussed with respect to these pathways

Summary

Introduction

Osteoarthritis (OA) is the most common degenerative joint disorder worldwide and its incidence rises with age (Loeser et al, 2012). The economic and societal burden due to costs of symptomatic treatment, inability to work, joint replacement surgery (and coinciding implant infections), rehabilitation, and social isolation is huge (Bijlsma et al, 2011; Le et al, 2012). Identifying the main molecular mechanisms by which OA is initiated and progresses is still one of the biggest challenges in this field. Despite the diversity of initial triggers OA disease progression follows a predictable cell. Joint immobility, and speed of disease progression are some of the few patientvariable parameters. While there is a lack of treatment options that are disease-modifying and improve joint-tissue homeostasis.

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