Mechanical stress regulates bone regulatory gene expression independent of estrogen and vitamin D deficiency in rats.

Abstract

Mechanical stress determines bone mass and structure. It is not known whether mechanical loading affects expression of bone regulatory genes in a combined deficiency of estrogen and vitamin D. We studied the effect of mechanical loading on the messenger RNA (mRNA) expression of bone regulatory genes during vitamin D and/or estrogen deficiency. We performed a single bout in vivo axial loading with 14 N peak load, 2 Hz frequency and 360 cycles in right ulnae of nineteen weeks old female control Wistar rats with or without ovariectomy (OVX), vitamin D deficiency and the combination of OVX and vitamin D deficiency (N = 10/group). Total bone RNA was isolated 6 hours after loading, and mRNA expression was detected of Mepe, Fgf23, Dmp1, Phex, Sost, Col1a1, Cyp27b1, Vdr, and Esr1. Serum levels of 25(OH)D, 1,25(OH)2 D and estradiol were also measured at this time point. The effect of loading, vitamin D and estrogen deficiency and their interaction on bone gene expression was tested using a mixed effect model analysis. Mechanical loading significantly increased the mRNA expression of Mepe, and Sost, whereas it decreased the mRNA expression of Fgf23 and Esr1. Mechanical loading showed a significant interaction with vitamin D deficiency with regard to mRNA expression of Vdr and Esr1. Mechanical loading affected gene expression of Mepe, Fgf23, Sost, and Esr1 independently of vitamin D or estrogen, indicating that mechanical loading may affect bone turnover even during vitamin D deficiency and after menopause.

• Authors: Ashwini Kumar Nepal, Huib W van Essen, Albert J van der Veen, Wessel N van Wieringen, Andrea W D Stavenuiter, Ferdy Kurniawan Cayami, Gerard Pals, Dimitra Micha, Dirk Vanderschueren, Paul Lips, Nathalie Bravenboer
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 39 Issue 1 Pg. 42-52 (01 2021) ISSN: 1554-527X [Electronic] United States
• PMID: 32530517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

Chemical References

• Bone Morphogenetic Proteins
• Estrogen Receptor alpha
• Estrogens
• Extracellular Matrix Proteins
• Fgf23 protein, rat
• Genetic Markers
• Mepe protein, rat
• Phosphates
• Sost protein, rat
• Fibroblast Growth Factors
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Topics

• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (metabolism)
• Animals
• Bone Morphogenetic Proteins (metabolism)
• Bone and Bones (metabolism)
• Estrogen Receptor alpha (metabolism)
• Estrogens (deficiency)
• Extracellular Matrix Proteins (metabolism)
• Female
• Fibroblast Growth Factors (metabolism)
• Gene Expression Regulation
• Genetic Markers
• Phosphates (metabolism)
• Rats, Wistar
• Stress, Mechanical
• Vitamin D Deficiency (metabolism)
• Rats