Load-induced regulation of tendon homeostasis by SPARC, a genetic predisposition factor for tendon and ligament injuries.

Autor:	Wang T; Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Western Australia 6009,Australia.; Division of Orthopaedic Surgery, Department of Surgery, Guangdong Provincial People'sHospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510000, China., Wagner A; Institute of Tendon and Bone Regeneration, Paracelsus Medical University-Spinal Cord Injury and Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria.; Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria., Gehwolf R; Institute of Tendon and Bone Regeneration, Paracelsus Medical University-Spinal Cord Injury and Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria.; Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria., Yan W; State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China., Passini FS; University Hospital Balgrist, University of Zurich, Zürich, Switzerland.; Institute for Biomechanics, ETH Zurich, 8008 Zürich, Switzerland., Thien C; Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Western Australia 6009,Australia., Weissenbacher N; Institute of Tendon and Bone Regeneration, Paracelsus Medical University-Spinal Cord Injury and Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria.; Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria., Lin Z; Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Western Australia 6009,Australia.; Division of Orthopaedic Surgery, Department of Surgery, Guangdong Provincial People'sHospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510000, China., Lehner C; Institute of Tendon and Bone Regeneration, Paracelsus Medical University-Spinal Cord Injury and Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria.; Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria., Teng H; Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210008, China., Wittner C; Computed Tomography Research Group, University of Applied Sciences Upper Austria, 4600 Wels, Austria., Zheng Q; Division of Orthopaedic Surgery, Department of Surgery, Guangdong Provincial People'sHospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510000, China., Dai J; State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China., Ni M; Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Western Australia 6009,Australia.; Department of Orthopaedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, China., Wang A; Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Western Australia 6009,Australia., Papadimitriou J; Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Western Australia 6009,Australia.; PathWest Laboratories, Nedlands, Western Australia 6009, Australia., Leys T; Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Western Australia 6009,Australia., Tuan RS; Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.; Institute for Tissue Engineering and Regenerative Medicine, Chinese University of Hong Kong, Hong Kong SAR, China., Senck S; Computed Tomography Research Group, University of Applied Sciences Upper Austria, 4600 Wels, Austria., Snedeker JG; University Hospital Balgrist, University of Zurich, Zürich, Switzerland.; Institute for Biomechanics, ETH Zurich, 8008 Zürich, Switzerland., Tempfer H; Institute of Tendon and Bone Regeneration, Paracelsus Medical University-Spinal Cord Injury and Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria.; Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria., Jiang Q; State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. andreas.traweger@pmu.ac.at minghao.zheng@uwa.edu.au qingj@nju.edu.cn., Zheng MH; Centre for Orthopaedic Translational Research, Medical School, University of Western Australia, Nedlands, Western Australia 6009,Australia. andreas.traweger@pmu.ac.at minghao.zheng@uwa.edu.au qingj@nju.edu.cn.; Perron Institute for Neurological and Translational Science, Nedlands, Western Australia 6009, Australia., Traweger A; Institute of Tendon and Bone Regeneration, Paracelsus Medical University-Spinal Cord Injury and Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria. andreas.traweger@pmu.ac.at minghao.zheng@uwa.edu.au qingj@nju.edu.cn.; Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2021 Feb 24; Vol. 13 (582).
DOI:	10.1126/scitranslmed.abe5738
Abstrakt:	Tendons and tendon interfaces have a very limited regenerative capacity, rendering their injuries clinically challenging to resolve. Tendons sense muscle-mediated load; however, our knowledge on how loading affects tendon structure and functional adaption remains fragmentary. Here, we provide evidence that the matricellular protein secreted protein acidic and rich in cysteine (SPARC) is critically involved in the mechanobiology of tendons and is required for tissue maturation, homeostasis, and enthesis development. We show that tendon loading at the early postnatal stage leads to tissue hypotrophy and impaired maturation of Achilles tendon enthesis in Sparc -/- mice. Treadmill training revealed a higher prevalence of spontaneous tendon ruptures and a net catabolic adaptation in Sparc -/- mice. Tendon hypoplasia was attenuated in Sparc -/- mice in response to muscle unloading with botulinum toxin A. In vitro culture of Sparc -/- three-dimensional tendon constructs showed load-dependent impairment of ribosomal S6 kinase activation, resulting in reduced type I collagen synthesis. Further, functional calcium imaging revealed that lower stresses were required to trigger mechanically induced responses in Sparc -/- tendon fascicles. To underscore the clinical relevance of the findings, we further demonstrate that a missense mutation (p.Cys130Gln) in the follistatin-like domain of SPARC , which causes impaired protein secretion and type I collagen fibrillogenesis, is associated with tendon and ligament injuries in patients. Together, our results demonstrate that SPARC is a key extracellular matrix protein essential for load-induced tendon tissue maturation and homeostasis. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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