Hyperglycemia induces osteogenic differentiation of bone marrow derived stem cells: an in vitro study

Abstract

Introduction: The physiopathology of calcific tendinopathy (CT) is largely unknown. It could be the result of an active cell-mediated process. Many endocrine and metabolic diseases may impair the homeostasis of the tendon. The present study investigated whether hyperglycemia may influence the differentiation of bone marrow MSCs (bMSCs). The hypothesis is that high glucose levels may induce bone differentiation of MSCs. Methods: Bone marrow (BM) was aspirated from the humeral head of three patients and concentrated. bMSCs were taken to the lab, counted, plated and grown to confluence. After 24 hrs cells were treated with MEM supplemented with low (5.0 mM), physiological (10 m M) and high (25 mM) glucose, (+) and (-) 10 m M insulin. Control cells were treated with MEM alone. Quantitative polymerase chain reaction (qPCR) was used to measure changes in gene expression levels specific for fibrocartilage in bMSCs. Results: After 7 days, a significantly increased gene expression of collagen type I, type II, alkaline phosphatase and osteopontin was found in bMSCs supplemented with high glucose compared both to control group, and to low and physiological glucose groups with and without insulin (p<0.05). When insulin was added to high glucose culture, a significantly higher expression of aggrecan, alkaline phosphatase, type I and II collagen, and fibronectin was found compared to all the other groups (p<0.05). Conclusion: When cultured in a high glucose medium, bMSCs express bone markers, and are able to differentiate toward an osteoblast lineage. CT may be caused by erroneous differentiation of MSCs in presence of high glucose serum levels.

Insertional Calcific Tendinopathy of the Achilles Tendon and Dysmetabolic Diseases: An Epidemiological Survey

“…differentiation is remarkable when MSCs are cultured with insulin too. 23 Oliva et al 24 recently focused on thyroid disorders and ruptures of rotator cuff tendons. A higher incidence of rotator cuff tears has been reported in patients with hypothyroidism, probably because of different proliferation capability of tenocytes in the presence of thyroid hormones.…”

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

“…115 In addition, in vitro insulin treatment of TSPCs increased the formation of mineralization modules and increased the expression of osteogenic genes such as Runx2, ALP, and osteonectin (OSN). 112,116 Thus, TSPCs derived from diabetic rat tendons demonstrate enhanced osteogenic and chondrogenic differentiation and suppressed tenogenic differentiation, which are likely to affect the tendon repair and facilitate the progression of diabetic tendinopathy. An in vitro study by Xu et al, reported that increased AGEs reduced cell viability, increased apoptosis and autophagy, induced senescence, and enhanced ossification in mouse Achilles TSPCs (Figure 1).…”