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Stochastic resonance in osteogenic response to mechanical loading ¹

Department of Orhopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA

²Correspondence: Indiana University, 541 Clinical Dr., Rm. 600, Indianapolis, IN 46202, USA. E-mail: turnerch{at}iupui.edu

SPECIFIC AIMS

A phenomenon called stochastic resonance, in which vibration enhances the response of a nonlinear system to a weak signal, has been observed in various biological sensory systems, suggesting that mechanosensation can be enhanced by with the addition of low-amplitude, broad-frequency vibration noise. We speculated that the osteogenic response of bone to the mechanical loading might be enhanced by stochastic resonance. If so, one could design new exercises for elderly people to build their bone mass and help prevent osteoporosis. We conducted studies to see whether bone formation in mice could be improved by stochastic resonance.

PRINCIPAL FINDING

1. The osteogenic response to mechanical loading is enhanced greatly by addition of vibration noise
Stochastic resonance has been reported in a variety of biological systems including, crayfish, shark, cricket, and human. Studies of human touch receptors suggest that mechanoreception can be enhanced through stochastic resonance. We showed previously that low-amplitude, broad-frequency vibration enhanced the expression of osteocalcin mRNA when combined with a high-amplitude, low-frequency sinusoidal loading signal applied to osteoblastic cells in culture. These results suggest that stochastic resonance might be used to enhance mechanosensation in bone tissue in vivo.

To test this possibility, we applied the following mechanical loading patterns to the right ulna of adult mice: 1) high-amplitude, low-frequency sinusoidal wave at 2 Hz with 3 N peak-to-peak, mimicking mechanical loading induced by exercise; 2) low-amplitude, broad-frequency vibration (Gaussian quasi-white noise at 0–50 Hz with 0.3 N mean amplitude); 3) the sinusoidal wave (exercise) combined with vibration to induce stochastic resonance (Fig. 1 ). The simulated exercise was applied for 30 s/day for 2 consecutive days. The osteogenic responses to regular exercise (2 Hz loading) and stochastic resonance exercise were measured using double-label histomorphometry.

View larger version (23K): [in this window] [in a new window]   Figure 1. Load waveforms applied to mouse ulnae. a) Sinusoidal wave at 2 Hz with 3.0 N peak-to-peak amplitude to mimic exercise; b) vibration (Gaussian quasi-white noise with a range of 0–50 Hz and a mean amplitude of 0.3 N); c) combined exercise with vibration. Feedback-controlled piezoelectric actuators were used to deliver loading to the mouse forearm.

Low-amplitude, broad-frequency vibration by itself had no effect on bone formation but, when added to exercise, vibration enhanced the osteogenic response at the periosteal surface of the bone by almost fourfold. Bone formation rate (rBFR/BS) at the periosteal surface of the ulna was increased 3.9-fold (P<0.0001) when noise was added to exercise compared with bone formation rates induced by exercise alone (Fig. 2 ).

View larger version (13K): [in this window] [in a new window]   Figure 2. Comparison between loading groups for relative bone formation parameters on the periosteal surface in ulnar sections. Histomorphometric measurements included mineralizing surface (rMS/BS), mineral apposition rate (rMAR), and bone formation rate (rBFR/BS). These parameters represent relative values, which were determined by subtracting the parameters in the left ulna (no loading) from those in the right ulna (loaded). Sinusoidal loading (exercise) and sine loading plus vibration (S+V) had significant osteogenic effects on the mouse ulna. No osteogenic effect was observed when vibration was applied without sine loading. The S+V-stimulated group had almost fourfold higher values of periosteal bone formation than the sine-stimulated group. Data represent the mean ± SE. *P < 0.05, **P < 0.01, ****P < 0.0001.

CONCLUSION AND SIGNIFICANCE

Both sine loading and sine plus vibration (S+V) loading promoted new bone formation in the mouse ulna. However, S+V induced almost fourfold more bone formation than sine stimulation on the periosteal surface. These results demonstrate that new bone formation in response to simulated exercise (sine loading) can be enhanced by adding low-amplitude, broad-frequency vibration, suggesting an effect of stochastic resonance. Calcium channels and other ion channels play fundamental roles in osteoblastic responses to external mechanical forces; it has been proposed that certain ion channels exhibit stochastic resonance, suggesting a possible molecular mechanism for stochastic resonance in bone.

It is possible that stochastic resonance can be exploited to enhance the osteogenic effects of exercise. Exercise can improve bone mass and bone strength in growing children and adolescents, but the osteogenic potential of exercise diminishes greatly after puberty. The adult skeleton is only moderately responsive to mechanical loading, and this responsiveness decreases with age. Vibration exercise is a promising new technique for stimulating bone formation in the aging skeleton. Our results demonstrate a potent effect on cortical bone formation when low-amplitude vibration is combined with simulated exercise. Cortical bone provides the majority of the biomechanical support in long bones and clinically important sites like the proximal femur. This application of stochastic resonance offers a new way to enhance bone formation where it is biomechanically most important.

View larger version (12K): [in this window] [in a new window]   Figure 3. Schematic diagram: Stochastic resonance in the osteogenic response to mechanical loading. Osteogenic effect of exercise (low-frequency sinusoidal loading) was increased by fourfold when vibration was added, though vibration by itself did not induce new bone formation. This suggests the osteogenic effect of mechanical loading can be enhanced through stochastic resonance in which added noise enhances the system response to an ordinary stimulus.

FOOTNOTES

¹ To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.02-0561fje; to cite this article, use FASEB J. (December 3, 2002) 10.1096/fj.02-0561fje

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This Article Full Text (PDF) All Versions of this Article: 17/2/313 02-0561fjev1    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by TANAKA, S. M. Articles by TURNER, C. H. Search for Related Content PubMed PubMed Citation Articles by TANAKA, S. M. Articles by TURNER, C. H.