Analysis of "old" proteins unmasks dynamic gradient of cartilage turnover in human limbs.

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Date

2019-10

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Abstract

Unlike highly regenerative animals, such as axolotls, humans are believed to be unable to counteract cumulative damage, such as repetitive joint use and injury that lead to the breakdown of cartilage and the development of osteoarthritis. Turnover of insoluble collagen has been suggested to be very limited in human adult cartilage. The goal of this study was to explore protein turnover in articular cartilage from human lower limb joints. Analyzing molecular clocks in the form of nonenzymatically deamidated proteins, we unmasked a position-dependent gradient (distal high, proximal low) of protein turnover, indicative of a gradient of tissue anabolism reflecting innate tissue repair capacity in human lower limb cartilages that is associated with expression of limb-regenerative microRNAs. This association shows a potential link to a capacity, albeit limited, for regeneration that might be exploited to enhance joint repair and establish a basis for human limb regeneration.

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Extremities, Cartilage, Articular, Humans, Osteoarthritis, Collagen, Fibronectins, Proteome, MicroRNAs, Regeneration, Half-Life, Databases, Factual, Mass Spectrometry, Cartilage Oligomeric Matrix Protein

Citation

Published Version (Please cite this version)

10.1126/sciadv.aax3203

Publication Info

Hsueh, Ming-Feng, Patrik Önnerfjord, Michael P Bolognesi, Mark E Easley and Virginia B Kraus (2019). Analysis of "old" proteins unmasks dynamic gradient of cartilage turnover in human limbs. Science advances, 5(10). p. eaax3203. 10.1126/sciadv.aax3203 Retrieved from https://hdl.handle.net/10161/34706.

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Scholars@Duke

Bolognesi

Michael Paul Bolognesi

Virginia Flowers Baker Distinguished Professor of Orthopaedic Surgery

As chief of the adult reconstruction service, the majority of my research effort has been directed toward clinical outcomes, implant survivorship, functional recovery, the biology of hip and knee arthritis and cost effectiveness.

Easley

Mark Erik Easley

Associate Professor of Orthopaedic Surgery
Kraus

Virginia Byers Kraus

Professor of Medicine

Virginia Byers Kraus, MD, PhD, is the Mary Bernheim Distinguished Professor of Medicine, Professor of Orthopaedic Surgery, Professor of Pathology and a faculty member of the Duke Molecular Physiology Institute in the Duke University School of Medicine. She is a practicing Rheumatologist with over 30 years’ experience in translational musculoskeletal research focusing on osteoarthritis, the most common of all arthritides. She trained at Brown University (ScB 1979), Duke University (MD 1982, PhD 1993) and the Duke University School of Medicine (Residency in Internal Medicine and Fellowship in Rheumatology). Her career has focused on elucidating osteoarthritis pathogenesis and translational research into the discovery and validation of biomarkers for early osteoarthritis detection, prediction of progression, monitoring of disease status, and facilitation of therapeutic developments. She is co-PI of the Foundation for NIH Biomarkers Consortium Osteoarthritis project. Trained as a molecular biologist and a Rheumatologist, she endeavors to study disease from bedside to bench.


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