TY - JOUR
T1 - Diabetic serum from older women increases adipogenic differentiation in mesenchymal stem cells
AU - Moseley, Kendall F.
AU - Doyle, Máire E.
AU - Jan De Beur, Suzanne M.
N1 - Funding Information:
This work was supported by the National Institutes of Health/National Institute on Aging, R03AG040695; Clinical research was conducted in the Johns Hopkins Bayview Clinical Research Unit, funded by the Institute for Clinical and Translational Research, UL1TR001079.
Publisher Copyright:
© 2018, © 2018 Taylor & Francis.
PY - 2018/7/3
Y1 - 2018/7/3
N2 - Background: Paradoxically, elderly persons with type 2 diabetes mellitus (T2DM) fracture despite having higher bone density than nondiabetics. Systemic factors associated with aging and T2DM may have detrimental, local effects on the skeleton. One such factor could be by altering the microenvironment of the mesenchymal stem cells (MSCs), multipotent progenitors capable of differentiating into adipocytes or osteoblasts. Methods: Sera were obtained from four participant groups (n = 40 total, 10 per group): (1) young women with normal glucose tolerance (NGTY), (2) postmenopausal women with NGT), (3) postmenopausal women with impaired glucose tolerance (IGT), and (4) postmenopausal women with T2DM. Sera were incubated with human MSCs for 14 days. Cell proliferation and apoptosis were measured using EdU and TUNEL labeling assays, respectively. MSC differentiation for each group was determined using osteogenic and adipogenic gene expression markers quantified by qRT-PCR, as well as Alizarin Red and Oil Red O staining. Results: Expression of adipogenic genes was greater than twofold higher (P < 0.05) in MSCs cultured with T2DM sera compared to those incubated with NGTY, NGT, or IGT sera. The increase in adipogenic gene expression corresponded with increased Oil Red O staining. Despite the increased adipogenic differentiation of MSCs exposed to T2DM sera, cell proliferation and apoptosis rates as well as osteoblastic activity were not significantly different among the four conditions. Conclusions: Systemic, circulating factors in the serum of older women with T2DM may promote MSC differentiation into adipocytes versus osteoblasts. Increased differentiation of MSCs into adipocytes is one possible mechanism by which T2DM increases fracture risk.
AB - Background: Paradoxically, elderly persons with type 2 diabetes mellitus (T2DM) fracture despite having higher bone density than nondiabetics. Systemic factors associated with aging and T2DM may have detrimental, local effects on the skeleton. One such factor could be by altering the microenvironment of the mesenchymal stem cells (MSCs), multipotent progenitors capable of differentiating into adipocytes or osteoblasts. Methods: Sera were obtained from four participant groups (n = 40 total, 10 per group): (1) young women with normal glucose tolerance (NGTY), (2) postmenopausal women with NGT), (3) postmenopausal women with impaired glucose tolerance (IGT), and (4) postmenopausal women with T2DM. Sera were incubated with human MSCs for 14 days. Cell proliferation and apoptosis were measured using EdU and TUNEL labeling assays, respectively. MSC differentiation for each group was determined using osteogenic and adipogenic gene expression markers quantified by qRT-PCR, as well as Alizarin Red and Oil Red O staining. Results: Expression of adipogenic genes was greater than twofold higher (P < 0.05) in MSCs cultured with T2DM sera compared to those incubated with NGTY, NGT, or IGT sera. The increase in adipogenic gene expression corresponded with increased Oil Red O staining. Despite the increased adipogenic differentiation of MSCs exposed to T2DM sera, cell proliferation and apoptosis rates as well as osteoblastic activity were not significantly different among the four conditions. Conclusions: Systemic, circulating factors in the serum of older women with T2DM may promote MSC differentiation into adipocytes versus osteoblasts. Increased differentiation of MSCs into adipocytes is one possible mechanism by which T2DM increases fracture risk.
KW - Aging
KW - bone density
KW - fracture
KW - mesenchymal stem cell
KW - type 2 diabetes mellitus
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U2 - 10.1080/07435800.2018.1441868
DO - 10.1080/07435800.2018.1441868
M3 - Article
C2 - 29521566
AN - SCOPUS:85043352238
SN - 0743-5800
VL - 43
SP - 155
EP - 165
JO - Endocrine Research
JF - Endocrine Research
IS - 3
ER -