|
|
Bioprocess 2023
骨钙素与葡萄糖代谢、能量代谢的研究进展
|
Abstract:
骨钙素(OCN)是一种源自成骨细胞的非胶原蛋白，具有多种激素特征。动物和实验模型表明，骨钙素被释放到血液中，能够对胰腺细胞和脂肪组织产生生物学效应。近些年来，研究者们开始把骨骼作为一个内分泌器官重视起来，发现未完全羧化的骨钙素(ucOC)具有一定的活性，能够在葡萄糖代谢及能量代谢中发挥不可或缺的作用，这使得骨钙素可能在代谢性疾病，如糖尿病、肥胖和代谢综合征中具有潜在的治疗意义。
Osteocalcin (OCN) is a non-collagenous protein derived from oste-oblasts with a variety of hormonal characteristics. Animal and experimental models have shown that osteocalcin is released into the bloodstream and is capable of producing biological effects on pancreatic cells and adipose tissue. In recent years, researchers have begun to focus on the skeleton as an endocrine organ, and have found that undercarboxylated osteocalcin (ucOC) is active and able to play an integral role in glucose metabolism and energy metabolism, which makes it potentially therapeutic in metabolic disorders such as diabetes mellitus, obesity, and metabolic syndrome.
| [1] | Lee, N.K., Sowa, H., Hinoi, E., et al. (2007) Endocrine Regulation of Energy Metabolism by the Skeleton. Cell, 130, 456-469. https://doi.org/10.1016/j.cell.2007.05.047 |
| [2] | Khosla, S. (2023) Evidence in Humans for Bone as an Endocrine Organ Regulating Energy Metabolism. Current Opinion in Endocrine and Metabolic Research, 31, Article ID: 100471. https://doi.org/10.1016/j.coemr.2023.100471 |
| [3] | Florencio-Silva, R., da Silva Sasso, G.R., Sasso-Cerri, E., Sim？es, M.J. and Cerri, P.S. (2015) Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. BioMed Research International, 2015, Article ID: 421746.
https://doi.org/10.1155/2015/421746 |
| [4] | Oldknow, K.J., Macrae, V.E. and Farquharson, C. (2015) Endocrine Role of Bone: Recent and Emerging Perspectives beyond Osteocalcin. Journal of Endocrinology, 225, R1-R19. https://doi.org/10.1530/JOE-14-0584 |
| [5] | Arias, C.F., Herrero, M.A., Echeverri, L.F., Oleaga, G.E. and López, J.M. (2018) Bone Remodeling: A Tissue-Level Process Emerging from Cell-Level Molecular Algorithms. PLOS ONE, 13, e0204171.
https://doi.org/10.1371/journal.pone.0204171 |
| [6] | Ferron, M. and Lacombe, J. (2014) Regulation of Energy Me-tabolism by the Skeleton: Osteocalcin and beyond. Archives of Biochemistry and Biophysics, 561, 137-146. https://doi.org/10.1016/j.abb.2014.05.022 |
| [7] | Fernandes, T.A.P., Gon？alves, L.M.L. and Brito, J.A.A. (2017) Relationships between Bone Turnover and Energy Metabolism. Journal of Diabetes Research, 2017, Article ID: 9021314. https://doi.org/10.1155/2017/9021314 |
| [8] | Confavreux, C.B. (2011) Bone: From a Reservoir of Miner-als to a Regulator of Energy Metabolism. Kidney International, 79, S14-S19. https://doi.org/10.1038/ki.2011.25 |
| [9] | Lin, X., Brennan-Speranza, T.C., Levinger, I. and Yeap, B.B. (2018) Un-dercarboxylated Osteocalcin: Experimental and Human Evidence for a Role in Glucose Homeostasis and Muscle Regula-tion of Insulin Sensitivity. Nutrients, 10, Article No. 847. https://doi.org/10.3390/nu10070847 |
| [10] | Hauschka, P.V., Lian, J.B., Cole, D.E. and Gundberg, C.M. (1989) Osteocalcin and Matrix Gla Protein: Vitamin K-Dependent Pro-teins in Bone. Physiological Reviews, 69, 990-1047. https://doi.org/10.1152/physrev.1989.69.3.990 |
| [11] | Ferron, M., Hinoi, E., Karsenty, G. and Ducy, P. (2008) Osteocalcin Differentially Regulates Beta Cell and Adipocyte Gene Ex-pression and Affects the Development of Metabolic Diseases in Wild-Type Mice. Proceedings of the National Academy of Sciences of the United States of America, 105, 5266-5270. https://doi.org/10.1073/pnas.0711119105 |
| [12] | Ng, K.W. and Martin, T.J. (2009) New Functions for Old Hormones: Bone as an Endocrine Organ. Molecular and Cellular Endocrinology, 310, 1-2. https://doi.org/10.1016/j.mce.2009.07.002 |
| [13] | Ducy, P., Zhang, R., Geoffroy, V., Ridall, A.L. and Karsenty, G. (1997) Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation. Cell, 89, 747-754. https://doi.org/10.1016/S0092-8674(00)80257-3 |
| [14] | Ducy, P., Desbois, C., Boyce, B., et al. (1996) Increased Bone Formation in Osteocalcin-Deficient Mice. Nature, 382, 448-452. https://doi.org/10.1038/382448a0 |
| [15] | Mizokami, A., Kawakubo-Yasukochi, T. and Hirata, M. (2017) Osteocalcin and Its Endocrine Functions. Biochemical Pharmacology, 132, 1-8. https://doi.org/10.1016/j.bcp.2017.02.001 |
| [16] | Kanazawa, I. (2015) Osteocalcin as a Hormone Regulating Glucose Metabolism. World Journal of Diabetes, 6, 1345-1354. https://doi.org/10.4239/wjd.v6.i18.1345 |
| [17] | Bilotta, F.L., Arcidiacono, B., Messineo, S., et al. (2018) Insulin and Osteocalcin: Further Evidence for a Mutual Cross-Talk. Endo-crine, 59, 622-632. https://doi.org/10.1007/s12020-017-1396-0 |
| [18] | Rosen, C.J. and Motyl, K.J. (2010) No Bones about It: Insulin Modulates Skeletal Remodeling. Cell, 142, 198-200.
https://doi.org/10.1016/j.cell.2010.07.001 |
| [19] | Otani, T., Mizokami, A., Kawakubo-Yasukochi, T., et al. (2020) The Roles of Osteocalcin in Lipid Metabolism in Adipose Tissue and Liver. Advances in Biological Regulation, 78, Arti-cle ID: 100752.
https://doi.org/10.1016/j.jbior.2020.100752 |
| [20] | Wei, J., Ferron, M., Clarke, C.J., et al. (2014) Bone-Specific Insu-lin Resistance Disrupts Whole-Body Glucose Homeostasis via Decreased Osteocalcin Activation. Journal of Clinical In-vestigation, 124, 1-13.
https://doi.org/10.1172/JCI72323 |
| [21] | Pandey, A., Khan, H.R., Alex, N.S., et al. (2020) Under-Carboxylated Os-teocalcin Regulates Glucose and Lipid Metabolism during Pregnancy and Lactation in Rats. Journal of Endocrinological Investigation, 43, 1081-1095.
https://doi.org/10.1007/s40618-020-01195-8 |
| [22] | Yamauchi, T., Kamon, J., Waki, H., et al. (2001) The Fat-Derived Hormone Adiponectin Reverses Insulin Resistance Associated with Both Lipoatrophy and Obesity. Nature Medicine, 7, 941-946. https://doi.org/10.1038/90984 |
| [23] | Yamauchi, T., Kamon, J., Ito, Y., et al. (2003) Cloning of Adiponectin Receptors That Mediate Antidiabetic Metabolic Effects. Nature, 423, 762-769. https://doi.org/10.1038/nature01705 |
| [24] | Tsuchida, A., Yamauchi, T., Ito, Y., et al. (2004) Insulin/Foxo1 Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity. Journal of Biological Chemistry, 279, 30817-30822.
https://doi.org/10.1074/jbc.M402367200 |
| [25] | Yamauchi, T., Nio, Y., Maki, T., et al. (2007) Targeted Disruption of AdipoR1 and AdipoR2 Causes Abrogation of Adiponectin Binding and Metabolic Actions. Nature Medicine, 13, 332-339. https://doi.org/10.1038/nm1557 |
| [26] | Otani, T., Mizokami, A., Hayashi, Y., et al. (2015) Signaling Path-way for Adiponectin Expression in Adipocytes by Osteocalcin. Cellular Signalling, 27, 532-544. https://doi.org/10.1016/j.cellsig.2014.12.018 |
| [27] | de Paula, F.J. and Rosen, C.J. (2013) Bone Remodeling and En-ergy Metabolism: New Perspectives. Bone Research, 1, 72-84. https://doi.org/10.4248/BR201301005 |
| [28] | Funakoshi, S., Yoshimura, K., Hirano, S., et al. (2020) Undercarbox-ylated Osteocalcin Correlates with Insulin Secretion in Japanese Individuals with Diabetes. Diabetology & Metabolic Syndrome, 12, Article No. 72.
https://doi.org/10.1186/s13098-020-00579-3 |
| [29] | Garanty-Bogacka, B., Syrenicz, M., Ra？, M., et al. (2013) Asso-ciation between Serum Osteocalcin, Adiposity and Metabolic Risk in Obese Children and Adolescents. Endokrynologia Polska, 64, 346-352.
https://doi.org/10.5603/EP.2013.0016 |
| [30] | Rodríguez-Narciso, S., Martínez-Portilla, R.J., Guzmán-Guzmán, I.P., et al. (2022) Osteocalcin Serum Concentrations and Markers of Energetic Metabolism in Pediatric Patients. Systematic Review and Metanalysis. Frontiers in Pediatrics, 10, Article 1075738. https://doi.org/10.3389/fped.2022.1075738 |
| [31] | Zheng, W.-B., Hu, J., Zhao, D.-C., et al. (2022) The Role of Os-teocalcin in Regulation of Glycolipid Metabolism and Muscle Function in Children with Osteogenesis Imperfecta. Fron-tiers in Endocrinology, 13, Article 898645.
https://doi.org/10.3389/fendo.2022.898645 |
| [32] | Ugurlu, I., Akalin, A. and Yorulmaz, G. (2022) The Association of Serum Osteocalcin Levels with Metabolic Parameters and Inflammation in Postmenopausal Women with Metabolic Syndrome. Metabolic Syndrome and Related Disorders, 20, 219-223. https://doi.org/10.1089/met.2021.0074 |
| [33] | Lei, H., Liu, J., Wang, W., et al. (2022) Association between Osteocal-cin, a Pivotal Marker of Bone Metabolism, and Secretory Function of Islet Beta Cells and Alpha Cells in Chinese Patients with Type 2 Diabetes Mellitus: An Observational Study. Diabetology & Metabolic Syndrome, 14, Article No. 160. https://doi.org/10.1186/s13098-022-00932-8 |
