Short-Term Exercise In Mice Increases Tibial Post-Yield Mechanical Properties While Two Weeks of Latency Following Exercise Increases Tissue-Level Strength

We have previously shown that exercise during growth increases post-yield deformation in C57BL6/129 (B6;129) male tibiae at the expense of reduced pre-yield deformation and structural and tissue strength. Other research in the literature indicates that increased mineral content, cross-sectional geometry and structural strength due to exercise can be maintained or increased after exercise ends for as long as 14 weeks. It was therefore hypothesized that after our exercise protocol ended, effects of exercise on mechanical properties would persist, resulting in increased post-yield behavior and rescued strength versus age-matched control mice. Beginning at 8 weeks of age, exercise consisted of running on a treadmill (30 min/day, 12 m/min, 5° incline) for 21 consecutive days. At the end of running and 2 weeks later, in the cortical bone of the tibial mid-diaphyses of B6;129 male mice, changes due to exercise and latency following exercise were assayed by mechanical tests and analyses of cross-sectional geometry. Exercise increased structural post-yield deformation compared with weight-matched control mice, without changes in bone size or shape, suggesting that exercised-induced changes in pre-existing bone quality were responsible. Over the 2-week latency period, no growth-related changes were noted in control mice, but exercise-induced changes resulted in increased tissue stiffness and strength versus mice sacrificed immediately after exercise ended. Our data indicate that periods of exercise followed by latency can alter strength, stiffness, and ductility of bone independent of changes in size or shape, suggesting that exercise may be a practical way to increase the quality of the bone extracellular matrix

Inbred Strain-Specific Response to Biglycan Deficiency in the Cortical Bone of C57BL6/129 and C3H/He Mice

Inbred strain-specific differences in mice exist in bone cross-sectional geometry, mechanical properties, and indices of bone formation. Inbred strain-specific responses to external stimuli also exist, but the role of background strain in response to genetic deletion is not fully understood. Biglycan (bgn) deficiency impacts bone through negative regulation of osteoblasts, resulting in extracellular matrix alterations and decreased mechanical properties. Because osteoblasts from C3H/He (C3H) mice are inherently more active versus osteoblasts from other inbred strains, and the bones of C3H mice are less responsive to other insults, it was hypothesized that C3H mice would be relatively more resistant to changes associated with bgn deficiency compared with C57BL6/129 (B6;129) mice. Changes in mRNA expression, tissue composition, mineral density, bone formation rate, cross-sectional geometry, and mechanical properties were studied at 8 and 11 wk of age in the tibias of male wildtype and bgn-deficient mice bred on B6;129 and C3H background strains. Bgn deficiency altered collagen cross-linking and gene expression and the amount and composition of mineral in vivo. In bgn's absence, changes in collagen were independent of mouse strain. Bgn-deficiency increased the amount of mineral in both strains, but changes in mineral composition, cross-sectional geometry, and mechanical properties were dependent on genetic background. Bgn deficiency influenced the amount and composition of bone in mice from both strains at 8 wk, but C3H mice were better able to maintain properties close to wildtype (WT) levels. By 11 wk, most properties from C3H knockout (KO) bones were equal to or greater than WT levels, whereas phenotypic differences persisted in B6;129 KO mice. This is the first study into mouse strain-specific changes in a small leucine-rich proteoglycan gene disruption model in properties across the bone hierarchy and is also one of the first to relate these changes to mechanical competence. This study supports the importance of genetic factors in determining the response to a gene deletion and defines biglycan's importance to collagen and mineral composition in vivo

Ultrastructural elastic deformation of cortical bone tissue probed by NIR Raman spectroscopy

Raman spectroscopy is used as a probe of ultrastructural (molecular) changes in both the mineral and matrix (protein and glycoprotein, predominantly type I collagen) components of murine cortical bone as it responds to loading in the elastic regime. At the ultrastructural level, crystal structure and protein secondary structure distort as the tissue is loaded. These structural changes are followed as perturbations to tissue spectra. We load tissue in a custom-made dynamic mechanical tester that fits on the stage of a Raman microprobe and can accept hydrated tissue specimens. As the specimen is loaded in tension and/or compression, the shifts in mineral P-O4v 1 and relative band heights in the Amide III band envelope are followed with the microprobe. Average load is measured using a load cell while the tissue is loaded under displacement control. Changes occur in both the mineral and matrix components of bone as a response to elastic deformation. We propose that the mineral apatitic crystal lattice is deformed by movement of calcium and other ions. The matrix is proposed to respond by deformation of the collagen backbone. Raman microspectroscopy shows that bone mineral is not a passive contributor to tissue strength. The mineral active response to loading may function as a local energy storage and dissipation mechanism, thus helping to protect tissue from catastrophic damage

Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice

Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which is independent of tissue quantity, suggests that deficiencies in tissue quality are responsible. However, the response to bgn-deficiency is inbred strain-specific. Mechanical loading influences bone matrix quality in addition to any increase in bone mass or change in bone formation activity. Since many diseases influence the mechanical integrity of bone through altered tissue quality, loading may be a way to prevent and treat extracellular matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response to mechanical loading vs. other inbred strains. It was therefore hypothesized that the bones from both wild type (WT) and KO B6;129 mice would be more responsive to exercise than the bones from C3H mice. To test these hypotheses at 11 weeks of age, following 21 consecutive days of exercise, we investigated cross-sectional geometry, mechanical properties, and tissue composition in the tibiae of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred strain-specific compositional and mechanical changes following exercise in WT and KO mice, and showed evidence of genotype-specific changes in bone in response to loading in a gene disruption model. This study further shows that exercise can influence bone tissue composition and/or mechanical integrity without changes in bone geometry. Together, these data suggest that exercise may represent a possible means to alter tissue quality and mechanical deficiencies caused by many diseases of bone

Dynamical Kohn Anomaly in Surface Acoustic Wave Response in Quantum Hall Systems Near ν=1/2\nu = 1/2

The dynamical analog of the Kohn Anomaly image of the Fermi Surface is demonstrated for the response functions to the surface acoustic waves in Quantum Hall Systems near $\nu = 1/2$. Kinks appear in the velocity shift $Delta s/s$ and attenuation coefficient $\Gamma$. The effect is considerably enhanced under periodic modulation and should be observable.Comment: 5 pages, 2 figures, the published versio