Autophagy guards tendon homeostasis
Abstract Tendons are vital collagen-dense specialized connective tissues transducing the force from skeletal muscle to the bone, thus enabling movement of the human body. Tendon cells adjust matrix turnover in response to physiological tissue loading and pathological overloading (tendinopathy). Neve...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04824-7 |
| _version_ | 1818523920781803520 |
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| author | Costanza Montagna Rene B. Svensson Monika L. Bayer Salvatore Rizza Emiliano Maiani Ching-Yan Chloé Yeung Giuseppe Filomeni Michael Kjær |
| author_facet | Costanza Montagna Rene B. Svensson Monika L. Bayer Salvatore Rizza Emiliano Maiani Ching-Yan Chloé Yeung Giuseppe Filomeni Michael Kjær |
| author_sort | Costanza Montagna |
| collection | DOAJ |
| description | Abstract Tendons are vital collagen-dense specialized connective tissues transducing the force from skeletal muscle to the bone, thus enabling movement of the human body. Tendon cells adjust matrix turnover in response to physiological tissue loading and pathological overloading (tendinopathy). Nevertheless, the regulation of tendon matrix quality control is still poorly understood and the pathogenesis of tendinopathy is presently unsolved. Autophagy, the major mechanism of degradation and recycling of cellular components, plays a fundamental role in the homeostasis of several tissues. Here, we investigate the contribution of autophagy to human tendons’ physiology, and we provide in vivo evidence that it is an active process in human tendon tissue. We show that selective autophagy of the endoplasmic reticulum (ER-phagy), regulates the secretion of type I procollagen (PC1), the major component of tendon extracellular matrix. Pharmacological activation of autophagy by inhibition of mTOR pathway alters the ultrastructural morphology of three-dimensional tissue-engineered tendons, shifting collagen fibrils size distribution. Moreover, autophagy induction negatively affects the biomechanical properties of the tissue-engineered tendons, causing a reduction in mechanical strength under tensile force. Overall, our results provide the first evidence that autophagy regulates tendon homeostasis by controlling PC1 quality control, thus potentially playing a role in the development of injured tendons. |
| first_indexed | 2024-12-11T05:50:44Z |
| format | Article |
| id | doaj.art-cc24ae1282b84b1d930ab8cd4ce6ec81 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-11T05:50:44Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-cc24ae1282b84b1d930ab8cd4ce6ec812022-12-22T01:18:49ZengNature Publishing GroupCell Death and Disease2041-48892022-04-0113411310.1038/s41419-022-04824-7Autophagy guards tendon homeostasisCostanza Montagna0Rene B. Svensson1Monika L. Bayer2Salvatore Rizza3Emiliano Maiani4Ching-Yan Chloé Yeung5Giuseppe Filomeni6Michael Kjær7Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital—Bispebjerg and FrederiksbergInstitute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital—Bispebjerg and FrederiksbergInstitute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital—Bispebjerg and FrederiksbergRedox Signaling and Oxidative Stress Group, Danish Cancer Society Research CenterUnicamillus-Saint Camillus, University of Health SciencesInstitute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital—Bispebjerg and FrederiksbergCenter for Healthy Aging, Department of Clinical Medicine, University of CopenhagenInstitute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital—Bispebjerg and FrederiksbergAbstract Tendons are vital collagen-dense specialized connective tissues transducing the force from skeletal muscle to the bone, thus enabling movement of the human body. Tendon cells adjust matrix turnover in response to physiological tissue loading and pathological overloading (tendinopathy). Nevertheless, the regulation of tendon matrix quality control is still poorly understood and the pathogenesis of tendinopathy is presently unsolved. Autophagy, the major mechanism of degradation and recycling of cellular components, plays a fundamental role in the homeostasis of several tissues. Here, we investigate the contribution of autophagy to human tendons’ physiology, and we provide in vivo evidence that it is an active process in human tendon tissue. We show that selective autophagy of the endoplasmic reticulum (ER-phagy), regulates the secretion of type I procollagen (PC1), the major component of tendon extracellular matrix. Pharmacological activation of autophagy by inhibition of mTOR pathway alters the ultrastructural morphology of three-dimensional tissue-engineered tendons, shifting collagen fibrils size distribution. Moreover, autophagy induction negatively affects the biomechanical properties of the tissue-engineered tendons, causing a reduction in mechanical strength under tensile force. Overall, our results provide the first evidence that autophagy regulates tendon homeostasis by controlling PC1 quality control, thus potentially playing a role in the development of injured tendons.https://doi.org/10.1038/s41419-022-04824-7 |
| spellingShingle | Costanza Montagna Rene B. Svensson Monika L. Bayer Salvatore Rizza Emiliano Maiani Ching-Yan Chloé Yeung Giuseppe Filomeni Michael Kjær Autophagy guards tendon homeostasis Cell Death and Disease |
| title | Autophagy guards tendon homeostasis |
| title_full | Autophagy guards tendon homeostasis |
| title_fullStr | Autophagy guards tendon homeostasis |
| title_full_unstemmed | Autophagy guards tendon homeostasis |
| title_short | Autophagy guards tendon homeostasis |
| title_sort | autophagy guards tendon homeostasis |
| url | https://doi.org/10.1038/s41419-022-04824-7 |
| work_keys_str_mv | AT costanzamontagna autophagyguardstendonhomeostasis AT renebsvensson autophagyguardstendonhomeostasis AT monikalbayer autophagyguardstendonhomeostasis AT salvatorerizza autophagyguardstendonhomeostasis AT emilianomaiani autophagyguardstendonhomeostasis AT chingyanchloeyeung autophagyguardstendonhomeostasis AT giuseppefilomeni autophagyguardstendonhomeostasis AT michaelkjær autophagyguardstendonhomeostasis |