Hyperglycemia impairs osteoblast cell migration and chemotaxis due to a decrease in mitochondrial biogenesis.

Heena, Pahwa and Touseef Khan, Md. and Kunal, Sharan (2020) Hyperglycemia impairs osteoblast cell migration and chemotaxis due to a decrease in mitochondrial biogenesis. Molecular and Cellular Biochemistry, 469. pp. 109-118. ISSN 0300-8177

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Abstract

Diabetes is associated with an increase in skeletal fragility and risk of fracture. However, the underlying mechanism for the same is not well understood. Specifcally, the results from osteoblast cell culture studies are ambiguous due to contradicting reports. The use of supraphysiological concentrations in these studies, unachievable in vivo, might be the reason for the same. Therefore, here, we studied the efect of physiologically relevant levels of high glucose during diabetes (11.1 mM) on MC3T3-E1 osteoblast cell functions. The results showed that high glucose exposure to osteoblast cells increases their diferentiation and mineralization without any efect on the proliferation. However, high glucose decreases their migratory potential and chemotaxis with a decrease in the associated cell signaling. Notably, this decrease in cell migration in high glucose conditions was accompanied by aberrant localization of Dynamin 2 in osteoblast cells. Besides, high glucose also caused a shift in mitochondrial dynamics towards the appearance of more fused and lesser fragmented mitochondria, with a concomitant decrease in the expression of DRP1, suggesting decreased mitochondrial biogenesis. In conclusion, here we are reporting for the frst time that hyperglycemia causes a reduction in osteoblast cell migration and chemotaxis. This decrease might lead to an inefcient movement of osteoblasts to the erosion site resulting in uneven mineralization and skeletal fragility found in type 2 diabetes patients, in spite of having normal bone mineral density (BMD).

Item Type:	Article
Uncontrolled Keywords:	Diabetes · Skeletal fragility · Osteoblast · Migration · Chemotaxis · Mitochondrial biogenesis
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 13 Molecular Biochemistry 600 Technology > 01 Medical sciences > 04 Diabetes Mellitus
Divisions:	Molecular Nutrition
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	03 Dec 2020 04:21
Last Modified:	03 Dec 2020 04:21
URI:	http://ir.cftri.res.in/id/eprint/14677

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