Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy

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.

Tendon stem/progenitor cell ageing: Modulation and rejuvenation

Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury.The role of tendon stem/progenitor cells(TSPCs)in tendon maintenance and regeneration has received increasing attention in recent years.The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect,or cause ageing,and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment.In this review,recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs,including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process,are analyzed.During the ageing process,TSPCs ageing might occur as a natural part of the tendon ageing,but could also result from decreased levels of growth factor,hormone deficits and changes in other related factors.Here,we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing,including moderate exercise,cell extracellular matrix condition,growth factors and hormones;these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.

Advanced glycation end productions and tendon stem/progenitor cells in pathogenesis of diabetic tendinopathy

Tendinopathy is a challenging complication observed in patients with diabetes mellitus.Tendinopathy usually leads to chronic pain,limited joint motion,and even ruptured tendons.Imaging and histological analyses have revealed pathological changes in various tendons of patients with diabetes,including disorganized arrangement of collagen fibers,microtears,calcium nodules,and advanced glycation end product(AGE)deposition.Tendon-derived stem/progenitor cells(TSPCs)were found to maintain hemostasis and to participate in the reversal of tendinopathy.We also discovered the aberrant osteochondrogenesis of TSPCs in vitro.However,the relationship between AGEs and TSPCs in diabetic tendinopathy and the underlying mechanism remain unclear.In this review,we summarize the current findings in this field and hypothesize that AGEs could alter the properties of tendons in patients with diabetes by regulating the proliferation and differentiation of TSPCs in vivo.