Maternal high-cholesterol diet negatively programs offspring bone development and downregulates hedgehog signaling in osteoblasts.

Ravi Mangu, S.V.S.S and Kalpana, Platel and Shinde, V. S. and Savitha, M. R. and Kunal, Sharan (2022) Maternal high-cholesterol diet negatively programs offspring bone development and downregulates hedgehog signaling in osteoblasts. Journal of Biological Chemistry, 298 (9). p. 102324.

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Abstract

Cholesterol is one of the essential intrauterine factors required for fetal growth and development. Maternal high cholesterol levels are known to be detrimental for offspring health. However, its long-term effect on offspring skeletal development remains to be elucidated. We performed our studies in two strains of mice (C57BL6/J and Swiss Albino) and human subjects (65 mother–female newborn dyads) to under�stand the regulation of offspring skeletal growth by maternal high cholesterol. We found that mice offspring from high�cholesterol-fed dams had low birth weight, smaller body length, and delayed skeletal ossification at the E18.5 embryonic stage. Moreover, we observed that the offspring did not recover from the reduced skeletal mass and exhibited a low bone mass phenotype throughout their life. We attributed this effect to reduced osteoblast cell activity with a concomitant increase in the osteoclast cell population. Our investigation of the mo�lecular mechanism revealed that offspring from high�cholesterol-fed dams had a decrease in the expression of li�gands and proteins involved in hedgehog signaling. Further, our cross-sectional study of human subjects showed a signifi�cant inverse correlation between maternal blood cholesterol levels and cord blood bone formation markers. Moreover, the bone formation markers were significantly lower in the female newborns of hypercholesterolemic mothers compared with mothers with normal cholesterolemic levels. Together, our results suggest that maternal high cholesterol levels deleteri�ously program offspring bone mass and bone quality and downregulate the hedgehog signaling pathway in their osteoblasts.

Item Type:	Article
Uncontrolled Keywords:	maternal high cholesterol levels, offspring, bone mass, bone quality, hedgehog signaling pathway, osteoblasts
Subjects:	500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 08 General Biochemistry
Divisions:	Dept. of Biochemistry Meat Fish and Poultry Technology Molecular Nutrition
Depositing User:	Food Sci. & Technol. Information Services
Date Deposited:	25 Jan 2023 05:30
Last Modified:	25 Jan 2023 05:30
URI:	http://ir.cftri.res.in/id/eprint/15874

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