Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy

Abstract

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.

Diabetes Mellitus and Obesity as Prognostic Factors in Arthroscopic Repair of Chronic Rotator Cuff Tears

“…This study, like previous before [ 13 , 14 , 16 ], supports the repair of chronic tendinopathy of the RC by arthroscopic techniques, with good long-term results for the most disabling symptoms of this injury: pain and deficit of shoulder function. The high level of satisfaction with the results obtained after the intervention is also noteworthy.…”

“…Lu P. et al use the term “diabetic tendinopathy” to refer to these alterations in tendon homeostasis in an attempt to understand the pathogenesis of diabetes in relation to the increased risk of rotator cuff tendon rupture after its repair [ 14 ]. Reinforcing this idea, Egemen O. et al, studied in animals the effects of diabetes on tissue regeneration, functionality, and histopathology in tendon injuries, observing a delay in regenerative capacity and recovery of functionality in the presence of diabetes compared with the control group [ 25 ].…”

“…Diabetes seems to be associated with an increased risk of rupture in chronic RC tendinopathies, as well as with a possible deficit in functional outcomes after arthroscopic tendon repair [ 13 ], but the results are inconclusive. High glucose environments seem to compromise the biomechanical properties of the diabetic tendons, as well as to produce relevant histopathological alterations, which eventually result in deficient tendon repair, maintenance, and remodeling [ 14 ].…”

Effect of Diabetes on Tendon Structure and Function: Not Limited to Collagen Crosslinking

“…A more detailed account of the effect of hyperglycemia and AGEs on tenocytes is provided in the review. 78 In addition to tenocytes, a small niche population of tendon stem progenitor cells (TSPCs) has been identified in many species. 79,106 TSPCs possess stem cell characteristics and play a significant role in tendon repair and regeneration.…”

New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors

“…Hong, Xu, Dai, & Zhao, 2016 ; Tesfaye & Selvarajah, 2012 ). Some studies show a positive correlation between both neuropathy harshness and poor glycemic control with both the consequence and intensity of DNP pain, relation with genetic predisposition that accurate ion channel variants may be inclined to the progression of painful DNP (P. P. Lu et al, 2020 ; Lukic, Humpert, Nawroth, & Bierhaus, 2008 ). Sensory neuron hyperexcitability in the form of impulsive movement and altered incentive response purpose is reported both in patients and in experimental models of DNP.…”