My piece is a comic showing a pink character introducing his friend Billy to the bone-derived hormone osteocalcin. The comic is meant to be a taste into what more can be learned about this hormone and hopefully leaves the reader wanting to find more research. The protagonist has a great appreciation for osteocalcin and is happy to share it with his friend. He covers the generalized functions of bones and then delves a bit deeper into the specific functions of osteocalcin as further explained in this essay.
Bones serve multiple functions for the human body. These include support, protection, movement, mineral and growth factor storage, blood cell formation, fat storage and hormone production. The hormone produced by bone is osteocalcin which is the subject of ongoing research into how it supports the body. Currently, there are multiple functions that this bone-derived hormone aids in including bone mineralization and controlling processes of the endocrine manner, whole body metabolism, reproduction, and cognition.
Osteocalcin is produced exclusively by osteoblasts and is the most abundant protein in the bone besides collagen. Despite being a hormone, osteocalcin does not function as a hormone. Instead, it aids in bone mineralization, glucose homeostasis, exercise capacity, brain development and male fertility. In recent years, osteocalcin has been found to have a hand in testosterone production, as it can stimulate the testes to increase testosterone production but not the ovaries to increase estrogen production (Kirmani et al., 2011). Due to this, male fertility can be impacted.
Previously, osteocalcin was thought to play a part in creating the matrix of the bone. Now, it has been found that osteocalcin helps to build the bone by filling the matrix of the bone through mineralization. This happens when mature osteocalcin is secreted in the bones internal environment where it changes to align it’s calcium binding Gla protein with other calcium ions to fill the matrix (Zoch et al., 2016).
Glucose metabolism is a frequently studied function of osteocalcin. This happens by osteocalcin stimulating insulin expression in the pancreas, and with adipocytes expressing the adiponectin, glucose can be better tolerated by the body (Kanazawa, 2015). Osteocalcin is the first bone-derived hormone known to impact exercise capacity. As humans exercise, more osteocalcin is produced, and while osteocalcin is also working to regulate the glucose metabolism, it is also signaling myofibers, fed by glucose and fatty acids, allowing for muscles function to increase (Mera et al., 2016). The connection between bones and muscles is further displayed in this way.
Brain development is another function of osteocalcin. It has been found to increase dopamine by binding to neurons in the ventral tegmental area which facilitates the synthesis of dopamine (Shan et al., 2019). Osteocalcin impacts the brain in other ways such as growth and increased function. Similar to dopamine production, osteocalcin works to increase other neurotransmitters like serotonin and norepinephrine while the synthesis of GABA is inhibited. While the extent of osteocalcin’s impact on memory and emotion is still being researched, one study found that mice lacking osteocalcin had increased anxiety behavior and depression. These mice also lacked a desire to explore and had more struggles with memory and learning than the mice with osteocalcin. In another study, systematic delivery of osteocalcin was shown to reverse age-related cognitive decline in mice (Khrimian et al., 2017). Osteocalcin secretion does decrease with age, and functions like glucose regulation, male fertility, and increased muscle function also decline with age, the full extent of correlation is not known but this could potentially explain why when osteocalcin is reintroduced the aging effects can be markedly reduced (Mera et al., 2016).
Kanazawa, I. (2015, December 25). Osteocalcin as a hormone regulating glucose metabolism. World journal of diabetes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4689779/.
Khrimian, L., Obri, A., & Karsenty, G. (2017, October 6). Modulation of cognition and anxiety-like behavior by bone remodeling. Molecular Metabolism. https://www.sciencedirect.com/science/article/pii/S2212877817306877#:~:text=In%20the%20brain%2C%20osteocalcin%20promotes,synthesis%20of%20these%20various%20neurotransmitters.
Kirmani, S., Atkinson, E. J., Melton, L. J., Riggs, B. L., Amin, S., & Khosla, S. (2011, August 19). Relationship of testosterone and osteocalcin levels during growth. American Society for Bone and Mineral Research. https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbmr.421.
Mera, P., Laue, K., Ferron, M., Confavreux, C., Wei, J., Galán-Díez, M., Lacampagne, A., Mitchell, S. J., Mattison, J. A., Chen, Y., Bacchetta, J., Szulc, P., Kitsis, R. N., de Cabo, R., Friedman, R. A., Torsitano, C., McGraw, T. E., Puchowicz, M., Kurland, I., & Karsenty, G. (2016, June 14). Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell metabolism. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910629/.
Shan, C., Ghosh, A., Guo, X.-zhi, Wang, S.-min, Hou, Y.-fang, Li, S.-tian, & Liu, J.-min. (2019, March 25). Roles for osteocalcin in brain signalling: implications in cognition- and motor-related disorders. Molecular Brain. https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-019-0444-5.
Zoch, M. L., Clemens, T. L., & Riddle, R. C. (2016, January). New insights into the biology of osteocalcin. Bone. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670816/.