Abstract
Osteocalcin, the most abundant member of the family of extracellular mineral binding gamma-carboxyglutamic acid proteins is synthesized primarily by osteoblasts. Its affinity for calcium ions is believed to limit bone mineralization. Several of the numerous hormones that regulate synthesis of osteocalcin, including glucocorticoids and parathyroid hormone, are also affected by stressful stimuli that require energy for an appropriate response. Based on our observations of OC responding to stressful sensory stimuli, the expression of OC in mouse and rat sensory ganglia was confirmed. It was thus hypothesized that the behavioral responses of the OC knockout mouse to stressful sensory stimuli would be abnormal. To test this hypothesis, behaviors related to sensory aspects of the stress response were quantified in nine groups of mice, aged 4–14 months, comparing knockout with their wild-type counterparts in six distinctly different behavioral tests. Resulting data indicated the following statistically significant differences: open field grooming frequency following saline injection, wild-type > knockout; paw stimulation with Von Frey fibers, knockout < wild-type; balance beam, knockout mobility < WT; thermal sensitivity to heat (tail flick), knockout < wild-type; and cold, knockout < wild-type. Insignificant differences in hanging wire test indicate that these responses are unrelated to reduced muscle strength. Each of these disparate environmental stimuli provided data indicating alterations of responses in knockout mice that suggest participation of osteocalcin in transmission of information about those sensory stimuli.
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Acknowledgments
The authors wish to thank Dale Buckendahl for fabricating the open field arena and von Frey testing chambers. We are grateful for the capable assistance of Nina Vaid, Young Kwang Kim and Teja Mehadashwar in behavioral observations. Work was supported by funds from the National Science Foundation, SGER Grant #0343515, the National Institutes of Health, National Institute for Alcoholism and Alcohol Abuse: R21 AA 12705-01, and R21 AA 14399-01A2 to PP-B, the New Jersey Commission on Spinal Cord Research: 10-3094-SCR-E-0, funds from the Aresty Foundation for Undergraduate Research (CF, AS, MS, AS, SP, DP, and SY), and from the Rutgers University Center of Alcohol Studies (LAP).
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Patterson-Buckendahl, P., Sowinska, A., Yee, S. et al. Decreased Sensory Responses in Osteocalcin Null Mutant Mice Imply Neuropeptide Function. Cell Mol Neurobiol 32, 879–889 (2012). https://doi.org/10.1007/s10571-012-9810-x
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DOI: https://doi.org/10.1007/s10571-012-9810-x