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1 Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA, USA
2 Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, CA, USA; Department of Medicine, Loma Linda University, Loma Linda, CA, USA
* To whom correspondence should be addressed. E-mail: subburaman.mohan{at}med.va.gov.
Our goal is to use QTL analysis to identify the genetic traits that contribute to variation in bone adaptive response to mechanical loading. Loads of varying magnitudes (6- 9N) were applied at 2Hz, 36cycles for 12 days on tibia of 10-week female B6 & C3H mice. 9N load on varying age groups. Changes in the bone parameters were measured using pQCT and gene expression by Real time PCR. Total vBMD was increased by 5% and 15%, respectively, at the 8 and 9N loads in the B6 mice, but not in the C3 mice. Periosteal circumference increased by 20% and 12%, respectively, which is reflected by a dramatic 44% and 26% increase in total area in the B6 and C3 mice. Bone response to bending showed no difference in the three age groups of the B6 and C3 mice. At day 2, mechanical loading caused significant down regulation in the expression of bone resorption (BR) marker genes with no change in the expression of bone formation (BF) marker genes. Four and eight days of loading caused 2-3 fold increases in the expression of BF genes (ColA1, ALP, OC, BSP) and 2-5 fold decreases in the expression of BR marker genes (MMP-9, TRAP). While expression of BF marker genes were up-regulated by 4-8 fold at 12 days of training, the expression levels of BR marker genes were up regulated by 7-9 fold. 4.point bending caused significantly greater changes in the expression levels of both BF and BR marker genes in the bones of the B6 mice compared to the C3 mice. Based on these data, we conclude that mechanical loading induced molecular pathways are activated to greater extent in B6 mice compared to C3 mice, ultimately resulting in a higher anabolic response in B6 mice.
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