The effects of high glucose condition on rat tenocytes <i>in vitro</i> and rat Achilles tendon <i>in vivo</i>

Ueda, Yasuhiro; Inui, Atsuyuki; Mifune, Yutaka; Sakata, Ryosuke; Muto, Tomoyuki; Harada, Yoshifumi; Tomita, Fumiaki; Kataoka, Tetsuro; Kokubu, Tatsuo; Kuroda, Ryosuke

doi:10.1302/2046-3758.75.bjr-2017-0126.r2

Cited by 37 publications

(71 citation statements)

References 54 publications

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“…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 . In contrast to these acute exposures studies, Wu et al reported that culturing rat AT cells in high (25 mM) glucose‐containing medium for 2 weeks did not alter the expression of Scx , Tnmd , or Col1 , but did decrease the expression of other tendon‐related genes including mohawk, biglycan, and transforming growth factor β‐1.…”

Section: Molecular Mechanisms Of Disrupted Homeostasis In T2dm Tendonsmentioning

confidence: 96%

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: 96%

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Nichols

Loiselle

2019

Journal Orthopaedic Research

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“…However, Ahmed et al [ 21 ] reported that diabetic tendons exhibited slightly smaller transverse areas than normal tendons, but showed no apparent alterations in the structural organization of collagen fibers. Ueda et al [ 42 ] showed that no significant difference was observed in fiber structure, fiber arrangement, rounding of the nuclei, or regional variations in cellularity between diabetic and nondiabetic Achilles tendons, but IHC staining of diabetic tendons demonstrated markedly increased NADPH oxidase (NOX) 1 expression within tenocytes compared with those of nondiabetic tendons, activating the production of reactive oxygen species (ROS) and resulting in tendon tissue damage.…”

Section: Histopathological Alterations In Diabetic Tendinopathymentioning

confidence: 99%

“…The main findings are summarized in Table 3 . Some researchers have shown that the proliferation of tenocytes is significantly decreased[ 42 ] and that cell migration, a crucial tenocyte function, is retarded under high glucose conditions[ 41 ]. Therefore, hyperglycemia might inhibit the ability of cells to repair damaged or degenerated tendons.…”

Section: Cytological and Molecular Alterations In Tenocytesmentioning

confidence: 99%

Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy

Chen

Dai

et al. 2020

WJSC

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There is accumulating evidence of an increased incidence of tendon disorders in people with diabetes mellitus. Diabetic tendinopathy is an important cause of chronic pain, restricted activity, and even tendon rupture in individuals. Tenocytes and tendon stem/progenitor cells (TSPCs) are the dominant cellular components associated with tendon homeostasis, maintenance, remodeling, and repair. Some previous studies have shown alterations in tenocytes and TSPCs in high glucose or diabetic conditions that might cause structural and functional variations in diabetic tendons and even accelerate the development and progression of diabetic tendinopathy. In this review, the biomechanical properties and histopathological changes in diabetic tendons are described. Then, the cellular and molecular alterations in both tenocytes and TSPCs are summarized, and the underlying mechanisms involved are also analyzed. A better understanding of the underlying cellular and molecular pathogenesis of diabetic tendinopathy would provide new insight for the exploration and development of effective therapeutics.

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“…Furthermore, a number of studies have demonstrated that hyperglycemic conditions induce oxidative stress and cytokine production, and they lead to in ammation and tissue damage in various organs [33,34,35]. Ueda et al reported the upregulation of the expression of mRNA for NOX1 and IL-6, and the production of ROS in HG conditions in tenocytes of the Achilles tendons in rats [36]. Previously published reports showed the main source of ROS is NOX and its activation increased ROS production [14,15,16].…”

Section: Discussionmentioning

confidence: 99%

Anti-oxidative effects of nicotinamide mononucleotide, a regulator of aging, on rat high glucose-induced tenocytes in vitro

Yamaura

Mifune

Inui

et al. 2020

Preprint

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Background Nicotinamide adenine dinucleotide (NAD+) plays an important role in energy metabolism, mitochondrial function, aging, and cell death. Nicotinamide mononucleotide (NMN) is one of the key precursors of NAD+. The purpose of this study is to evaluate the oxidative stress effects of NMN on rat tenocytes in-vitro.Methods Tenocytes from normal Sprague–Dawley rats were cultured in regular glucose (RG) and high-glucose (HG) conditions with or without NMN, and were divided into four groups: RG NMN−, RG NMN+, HG NMN−, and HG NMN+. Cell viability, reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expressions of NADPH oxidase (NOX) 1, NOX4, interleukin (IL)-6, SIRT1, and SIRT6, were determined in-vitro.Results The NMN groups led to significantly higher cell viabilities compared with the other groups. The mRNA expressions of NOX1, NOX4, and IL6, in the HG NMN+ group were significantly lower compared with those of the HG NMN− group. Conversely, the corresponding expressions of the SIRT1 and SIRT6 levels in the HG NMN+ group were significantly higher compared with those of the HG NMN−group. Both the accumulation of ROS and apoptosis in the HG NMN− group were significantly higher compared with those in the RG NMN− group at 48 h.Conclusion The expression levels of NOX1, NOX4, IL6, and ROS were significantly reduced by NMN. These results suggest that NMN could effectively reduce the oxidative stress by activating SIRT1 and SIRT6, and by inhibiting the activity of NOX and apoptosis in the tenocytes.

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The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo

Cited by 37 publications

References 54 publications

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Effects of Type II Diabetes Mellitus on Tendon Homeostasis and Healing

Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy

Anti-oxidative effects of nicotinamide mononucleotide, a regulator of aging, on rat high glucose-induced tenocytes in vitro

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