The effects of high glucose on tendon-derived stem cells: implications of the pathogenesis of diabetic tendon disorders

Lin, Yucheng; Li, Yingjuan; Menemenlis, Dimitris; Dai, Guang-Chun; Shi, Liu; Hua, Xu; Ni, Ming; Zhao, Song; Chen, Hui; Wang, Chen; Li, Gang; Teng, Gao‐Jun

doi:10.18632/oncotarget.15418

Cited by 54 publications

(57 citation statements)

References 36 publications

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“…A number of studies have evaluated the effects of culturing tendon cell in high glucose‐containing medium to determine potential cell‐mediated mechanisms for the mechanical deficits seen in T2DM tendons (Table ). Lin et al found that culturing rat patellar tendon cells in high (15 or 25 mM) glucose for up to 48 h lead to decreases in the expression of collagen type I ( Col1 ) and the tendon cell markers scleraxis ( Scx ) and tenomodulin ( Tnmd ), along with increased apoptosis and decreased proliferation compared to cells grown in low glucose (5.5 mM). In similar studies, Ueda et al and Tsai et al found that culturing rat AT cells in high glucose (33 and 25 mM, respectively) for up to 72 h elicited increased expression of catabolic enzymes (matrix metalloproteinases [ Mmp ] 2, 9, and 13) and the pro‐inflammatory cytokine interleukin‐6 .…”

Section: Molecular Mechanisms Of Disrupted Homeostasis In T2dm Tendonsmentioning

confidence: 99%

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Nichols

Loiselle

2019

Journal Orthopaedic Research

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Over 300,000 tendon repairs are performed annually in the United States to repair damage to tendons as a result of either acute trauma or chronic tendinopathy. Individuals with type II diabetes mellitus (T2DM) are four times more likely to experience tendinopathy, and up to five times more likely to experience a tendon tear or rupture than non‐diabetics. As nearly 10% of the US population is diabetic, with an additional 33% pre‐diabetic, this is a particularly problematic health care challenge. Tendon healing in general is challenging and often unsatisfactory due to the formation of mechanically inferior scar‐tissue rather than regeneration of native tendon structure. In T2DM tendons, there is evidence of an amplified scar tissue response, which may be associated with the increased the risk of rupture or impaired restoration of range of motion. Despite the dramatic effect of T2DM on tendon function and outcomes following injury, there are few therapies available to promote improved healing in these patients. Several recent studies have enhanced our understanding of the pro‐inflammatory environment of T2DM healing and have assessed potential treatment approaches to mitigate pathological progression in pre‐clinical models of diabetic tendinopathy. This review discusses the current state of knowledge of diabetic tendon healing from molecular to mechanical disruptions and identifies promising approaches and critical knowledge gaps as the field moves toward identification of novel therapeutic strategies to maintain or restore tendon function in diabetic patients. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:13–22, 2020

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Section: Molecular Mechanisms Of Disrupted Homeostasis In T2dm Tendonsmentioning

confidence: 99%

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Nichols

Loiselle

2019

Journal Orthopaedic Research

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“…Although we have not investigated the mechanism involved in pro-proliferative effects of insulin on TPCs, similar mechanisms are likely involved. On the other hand, Lin et al demonstrated that high glucose decreases in vitro TPC proliferation and induces apoptosis [21]. A subsequent study by the same group showed that TPCs isolated from rats with experimental diabetes had a decreased rate of in vitro proliferation compared to control TPCs.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, systemic hyperinsulinemia secondary to impaired insulin sensitivity can occur during early DM. While the tenogenic phenotype of TPCs in injured DM tendon tissue and during in vitro culture with high-glucose concentration is significantly decreased, the effects of highinsulin concentrations on TPCs have not been investigated [20,21]. Both exogenous insulin and recombinant insulinlike growth factor-I (IGF-I) increase the in vitro osteogenic capacity of osteoblasts and periodontal ligament fibroblasts [22,23].…”

Section: Introductionmentioning

confidence: 99%

Insulin Enhances the In Vitro Osteogenic Capacity of Flexor Tendon-Derived Progenitor Cells

Durgam

Altmann

Coughlin

et al. 2019

Stem Cells International

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There is increased incidence of tendon disorders and decreased tendon healing capacity in people with diabetes mellitus (DM). Recent studies have also suggested pathological ossification in repair tendon of people with DM. Therefore, the objective of this study is to investigate the effects of insulin supplementation, an important pathophysiologic stimulus of DM, on tendon progenitor cell (TPC) proliferation and in vitro osteogenic capacity. Passage 3 TPCs were isolated from collagenase-digested, equine superficial digital flexor tendons. TPC proliferation was measured via MTT assay after 3 days of monolayer culture in medium supplemented with 0, 0.007, 0.07, and 0.7 nM insulin. In vitro osteogenic capacity of TPCs (Alizarin Red staining, osteogenic mRNA expression, and alkaline phosphatase bioactivity) was assessed with 0, 0.07, and 0.7 nM insulin-supplemented osteogenic induction medium. Insulin (0.7 nM) significantly increased TPC proliferation after 3 days of monolayer culture. Alizarin Red staining of insulin-treated TPC osteogenic cultures demonstrated robust cell aggregation and mineralized matrix secretion, in a dose-dependent manner. Runx2, alkaline phosphatase, and Osteonectin mRNA and alkaline phosphatase bioactivity of insulin-treated TPC cultures were significantly higher at day 14 of osteogenesis compared to untreated controls. Addition of picropodophyllin (PPP), a selective IGF-I receptor inhibitor, mitigated the increased osteogenic capacity of TPCs, indicating that IGF-I signaling plays an important role. Our findings indicate that hyperinsulinemia may alter TPC phenotype and subsequently impact the quality of repair tendon tissue.

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“…Also, in vitro studies can be useful in understanding the mechanisms of tendon healing disorders in diabetes. Lin et al, determined the effect of various glucose concentrations on tendon‐derived stem cells (TDSCs) in vitro. It has been shown that high glucose concentration inhibits the proliferation of these cells, induces apoptosis and reduces the expression of markers associated with the tendons (sclerosis and collagen type 1 alpha 1 chain).…”

Section: Ligament and Tendon Injuries In Patients With Dmmentioning

confidence: 99%

Influence of diabetes on tissue healing in orthopaedic injuries

Stolarczyk

Sarzyńska

Gondek

et al. 2018

Clin Exp Pharma Physio

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Diabetes is a group of metabolic diseases characterized by hyperglycaemia resulting from the defective action or secretion of insulin. Chronic hyperglycaemia can lead to the damage, dysfunction and failure of various organs. In the context of complications of healing and orthopaedic rehabilitation, vascular (microangiopathy) and nerve (neuropathy) disorders deserve particular attention. About 12% of the patients admitted to orthopaedic departments have diabetes. Studies indicate that there is an indisputable link between diabetes and: an increased risk of fractures, the difficult healing of injuries of bones, ligaments and musculotendinous. It appears that one of the main reasons for this is non-enzymatic glycosylation (glycation) of collagen molecules, a phenomenon observed in the elderly and diabetic populations, as it leads to the formation of advanced glycation end products (AGEs). Collagen is one of the major connective tissue components, and is therefore part of ligaments, tendons and bones. AGEs affect the weakening of its structure and biomechanical properties, and thus also affects the weakening of the structure and properties of the above-mentioned tissues. The aim of the study is to undertake an overview of the current knowledge of the impact of diabetes on the risk of some injuries and subsequent healing and rehabilitation of patients following orthopaedic injuries.

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The effects of high glucose on tendon-derived stem cells: implications of the pathogenesis of diabetic tendon disorders

Cited by 54 publications

References 36 publications

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Insulin Enhances the In Vitro Osteogenic Capacity of Flexor Tendon-Derived Progenitor Cells

Influence of diabetes on tissue healing in orthopaedic injuries

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