Mechanical loading-induced gene expression and BMD changes are different in two inbred mouse strains.
Our goal is to evaluate skeletal anabolic response to mechanical loading in different age groups of C57B1/6J (B6) and C3H/HeJ (C3H) mice with variable loads using bone size, bone mineral density (BMD), and gene expression changes as end points. Loads of 6-9 N were applied at 2 Hz for 36 cycles for 12 days on the tibia of 10-wk-old female B6 and C3H mice. Effects of a 9-N load on 10-, 16-, and 36-wk-old C3H mice were also studied. Changes in bone parameters were measured using peripheral quantitative computed tomography, and gene expression was determined by real-time PCR. Total volumetric BMD was increased by 5 and 15%, respectively, with 8- and 9-N loads in the B6, but not the C3H, mice. Increases of 20 and 12% in periosteal circumference were reflected by dramatic 44 and 26% increases in total area in B6 and C3H mice, respectively. The bone response to bending showed no difference in the three age groups of B6 and C3H mice. At 2 days, mechanical loading resulted in significant downregulation in expression of bone resorption (BR), but not bone formation (BF) marker genes. At 4 and 8 days of loading, expression of BF marker genes (type I collagen, alkaline phosphatase, osteocalcin, and bone sialoprotein) was increased two- to threefold and expression of BR marker genes (matrix metalloproteinase-9 and thrombin receptor-activating peptide) was decreased two- to fivefold. Although expression of BF marker genes was upregulated four- to eightfold at 12 days of training, expression of BR marker genes was upregulated seven- to ninefold. Four-point bending caused significantly greater changes in expression of BF and BR marker genes in bones of the B6 than the C3H mice. We conclude that mechanical loading-induced molecular pathways are activated to a greater extent in the B6 than in the C3H mice, resulting in a higher anabolic response in the B6 mice.
Kesavan
Chandrasekhar
C
Musculoskeletal Disease Center, Veterans Affairs Loma Linda Healthcare System, Loma Linda, CA 92357, USA.
Mohan
Subburaman
S
Oberholtzer
Susanna
S
Wergedal
Jon E
JE
Baylink
David J
DJ
D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D015415:Biomarkers; D015519:Bone Density / Q000502:physiology*; D001862:Bone Resorption / Q000235:genetics* / Q000503:physiopathology*; D001842:Bone and Bones / Q000502:physiology*; D024042:Collagen Type I / Q000235:genetics; D005260:Female; D050723:Fractures, Bone / Q000503:physiopathology; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D015675:Osteocalcin / Q000235:genetics; D010521:Periosteum / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics; D013045:Species Specificity; D013314:Stress, Mechanical; D016474:Weight-Bearing / Q000502:physiology*
D015415:Biomarkers; D024042:Collagen Type I; D012795:Sialoglycoproteins; D015675:Osteocalcin; D000469:Alkaline Phosphatase