Abstract
Musculoskeletal dysfunctions are highly prevalent due to increasing life expectancy. Consequently, novel solutions to optimize treatment of patients are required. The current major research focus is to develop innovative concepts for single tissues. However, interest is also emerging to generate applications for tissue transitions where highly divergent properties need to work together, as in bone-cartilage or bone-tendon transitions. Finding medical solutions for dysfunctions of such tissue transitions presents an added challenge, both in research and in clinics. This review aims to provide an overview of the anatomical structure of healthy adult entheses and their development during embryogenesis. Subsequently, important scientific progress in restoration of damaged entheses is presented. With respect to enthesis dysfunction, the review further focuses on inflammation. Although molecular, cellular and tissue mechanisms during inflammation are well understood, tissue regeneration in context of inflammation still presents an unmet clinical need and goes along with unresolved biological questions. Furthermore, this review gives particular attention to the potential role of a signaling mediator protein, transforming growth factor beta-activated kinase-1 (TAK1), which is at the node of regenerative and inflammatory signaling and is one example for a less regarded aspect and potential important link between tissue regeneration and inflammation.
Highlights
The functionality of the musculoskeletal system is based on force transmission between muscles and bones, which are connected by tendons
No complete and functional solution to recreate the complex function and structure of entheses is available to date, which results in an unmet clinical need
Inflammatory responses could be subdued by applying transforming growth factor beta-activated kinase-1 (TAK1) inhibitors like Takinib or (5Z)-7-oxozeaenol
Summary
The functionality of the musculoskeletal system is based on force transmission between muscles and bones, which are connected by tendons. Due to the differential mechanical properties of elastic soft tendons and stiff hard bones, the attachment unit, called enthesis, needs to fulfil high compositional, organizational and mechanical requirements. These demanding properties make entheses an extraordinary and interesting tissue interface. Because of these interesting facts, several reviews have already been written about enthesis before [1,2,3]. In the first part of the present review, we give a short overview on the structure, development and physiology of this special tissue. We continue by summarizing tissue engineering strategies. The major part of the review is devoted to pinpointing the potential role of TAK1 as a future therapeutic target
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