Tendinopathy: injury, repair, and current exploration

Lipman, Kelsey; Wang, Chenchao; Ting, Kang; Soo, Chia; Zheng, Zhong

doi:10.2147/dddt.s154660

Cited by 115 publications

(133 citation statements)

References 133 publications

(187 reference statements)

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“…Few tendon-specific markers have been identified. Col-1a1 and Col-3a1 are considered to be the main tendon collagen in matrix [5], especially Col-1a1 which has often been used as a tendon-associated marker in tenogenic differentiation study [13,25]. Tnmd is a member of type II transmembrane glycoprotein.…”

Section: Discussionmentioning

confidence: 99%

“…Not only is tendon injury prevalent, it is also a tough clinic problem, due to its hard healing process because of hypovascularity and hypocellularity [3]. Many attempts, such as autologous grafting, application of growth factors and gene therapy, have been made to repair the injury, but often following the dysfunction of the donor site and a long and poor recovery [4,5]. Therefore, the treatment strategy to repair tendon injury still needed to be explored.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

Chen¹,

Zhang²,

Gu³

et al. 2020

Preprint

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Background: Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cells (MSCs) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to investigate the role of hypoxia in the tenogenic differentiation of MSCs in vitro and in vivo and to compare the tenogenic differentiation capacities of different MSCs under hypoxia condition in vitro. Methods: Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized by the expression of MSC-specific markers and tri-lineage differentiation. The expression of hypoxia induced factor-1 alpha (Hif-1α) and the proliferation of AMSCs and BMSCs were examined in order to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia and/or Tgf-β1 condition. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Results: Hypoxia remarkably increased the expression of Hif-1α and the proliferation of AMSCs and BMSCs. Our in vitro results detected that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group, but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than those of normoxic BMSCs, as evidenced by histological scores, quantitative analysis of immunohistochemical staining for Col-1a1 and Tnmd, the range and average of collagen fibril diameters and patellar tendon biomechanical tests. Conclusions: These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

Chen¹,

Zhang²,

Gu³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…In the United Kingdom, absenteeism due to lateral epicondylitis (tennis elbow) alone, is approximated to cost £27 million per annum (Walker-Bone et al, 2012). Furthermore, tendons and ligaments heal poorly frequently resulting in months of disability and weaker tendon(s) that are more susceptible to future injuries (Lipman et al, 2018;Riley, 2008). Despite our increased understanding of tendon biology and tendon repair mechanisms, we are yet to develop effective treatment strategies, and surgical outcomes are often poor (Coghlan et al, 2008;James et al, 2008;Kukkonen et al, 2014;Liu et al, 2008;Vitale et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of tendon and ligament injuries in Aotearoa/New Zealand between 2010 and 2016

et al. 2020

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Background: Injuries to tendons and ligaments make up a large portion of musculoskeletal injuries, and contribute to significant morbidity and healthcare costs. However, there is currently a poor understanding of the burden of these injuries at a population level. The purpose of this study was to quantify the burden and distribution of tendon and ligament injuries in the Aotearoa/New Zealand population. Methods: Using the Accident Compensation Corporation (ACC, a no fault comprehensive compensation scheme encompassing all of Aotearoa/New Zealand; population in 2013 4.4 million) database, data specific to tendon and ligament injuries were identified between July 2010 and June 2016. The total number of claims made and the total cost of these claims per financial year were analyzed. Injuries were categorized by anatomical site, gender, ethnicity and age of the claimant.Results: During the 6-year study period, the total number of tendon and ligament injury claims was 1,112,077, with a total cost of over $1.4 billion NZD. There was a 16.2% increase in the number of claims, and a 40% increase in the total cost of these injuries during this period. The majority of claims were made by people of European ethnicity, whilst the number of claims made by people of Asian ethnicity increased at the greatest rate; 52% (from 9047 claims in 2011) during the 6-year study period. Interestingly, Māori (Indigenous New Zealanders) maintained the highest average cost per claim ($1614.05 NZD); 13% more than the overall average cost per claim ($1262.12 NZD). The most common sites of injury were the shoulder and knee; these injuries were also the greatest contributors to overall cost. The total costs of injuries peaked in claimants aged 40-54, irrespective of the number of claims made for that age group.Conclusions: Health and economic burdens of tendon and ligament injuries in Aotearoa/New Zealand are rising. The high healthcare costs underscore the urgent need for multifaceted interventions to reduce the incidence and improve clinical outcomes of tendon and ligament injuries.

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“…Tendinopathy accounts for about 30% of all musculoskeletal complaints in a general practice setting [ 1 ]. Both acute and chronic tendinopathy cause pain and morbidity, and may require long and expensive treatments including joint replacement [ 2 ]. Recent studies have revealed the presence of a stem cell population within tendons [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Nudt21-mediated alternative polyadenylation of HMGA2 3′-UTR impairs stemness of human tendon stem cell

Sun

Chen

et al. 2020

Aging

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Tendon-derived stem cells (TSCs) play a primary role in tendon physiology, pathology, as well as tendon repair and regeneration after injury. TSCs are often exposed to mechanical loading-related cellular stresses such as oxidative stress, resulting in loss of stemness and multipotent differentiation potential. Cytoprotective autophagy has previously been identified as an important mechanism to protect human TSCs (hTSCs) from oxidative stress induced impairments. In this study, we found that high-mobility AT-hook 2 (HMGA2) overexpression protects hTSCs against H 2 O 2 -induced loss of stemness through autophagy activation. Evidentially, H 2 O 2 treatment increases the expression of Nudt21, a protein critical to polyadenylation site selection in alternative polyadenylation (APA) of mRNA transcripts. This leads to increased cleavage and polyadenylation of HMGA2 3′-UTR at the distal site, resulting in increased HMGA2 silencing by the microRNA let-7 and reduced HMGA2 expression. In conclusion, Nudt21-regulated APA of HMGA2 3′-UTR and subsequent HMGA2 downregulation mediates oxidative stress induced hTSC impairments.

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Tendinopathy: injury, repair, and current exploration

Cited by 115 publications

References 133 publications

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

Hypoxia promotes tenocyte differentiation of mesenchymal stem cells

Epidemiology of tendon and ligament injuries in Aotearoa/New Zealand between 2010 and 2016

Nudt21-mediated alternative polyadenylation of HMGA2 3′-UTR impairs stemness of human tendon stem cell

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