A novel nonosteocytic regulatory mechanism of bone modeling
| Autor: | Yulia Shwartz, Ron Shahar, Paul Zaslansky, Shelley Griess-Fishheimer, Lior Ofer, Elazar Zelzer, Shiri Kult, Mason N. Dean, Efrat Monsonego-Ornan, Janna Zaretsky |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Vertebrae Physiology Cell Oryzias Mechanotransduction Cellular 0302 clinical medicine Animal Cells Osteogenesis Medicine and Health Sciences Protein Isoforms Mechanotransduction Biology (General) Musculoskeletal System Zebrafish Connective Tissue Cells Feedback Physiological Regulation of gene expression biology PHASE CONTRAST MICROTOMOGRAPHY Applied Mathematics General Neuroscience Eukaryota Vertebrate Animal Models Biomechanical Phenomena Cell biology medicine.anatomical_structure Experimental Organism Systems Connective Tissue Osteichthyes Osteocyte Vertebrates Physical Sciences Bone Remodeling Anatomy Cellular Types General Agricultural and Biological Sciences BONE Research Article Fish Proteins PHASE CONTRAST Fish Biology QH301-705.5 Finite Element Analysis Research and Analysis Methods Osteocytes Bone and Bones Collagen Type I General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Model Organisms Chondrocytes Species Specificity biology.animal Fish Physiology medicine Animals Animal Physiology Humans Gene Process (anatomy) Swimming Glycoproteins FISH BONE Osteoblasts General Immunology and Microbiology Biological Locomotion Organisms Biology and Life Sciences Cell Biology Zebrafish Proteins biology.organism_classification Spine Vertebrate Physiology Biological Tissue Fish 030104 developmental biology Gene Expression Regulation Animal Studies Zoology Mathematics 030217 neurology & neurosurgery |
| Zdroj: | 'PLoS Biology ', vol: 17, pages: e3000140-1-e3000140-22 (2019) PLoS Biology, Vol 17, Iss 2, p e3000140 (2019) PLoS Biology |
| ISSN: | 1544-9173 |
| Popis: | Osteocytes, cells forming an elaborate network within the bones of most vertebrate taxa, are thought to be the master regulators of bone modeling, a process of coordinated, local bone-tissue deposition and removal that keeps bone strains at safe levels throughout life. Neoteleost fish, however, lack osteocytes and yet are known to be capable of bone modeling, although no osteocyte-independent modeling regulatory mechanism has so far been described. Here, we characterize a novel, to our knowledge, bone-modeling regulatory mechanism in a fish species (medaka), showing that although lacking osteocytes (i.e., internal mechanosensors), when loaded, medaka bones model in mechanically directed ways, successfully reducing high tissue strains. We establish that as in mammals, modeling in medaka is regulated by the SOST gene, demonstrating a mechanistic link between skeletal loading, SOST down-regulation, and intense bone deposition. However, whereas mammalian SOST is expressed almost exclusively by osteocytes, in both medaka and zebrafish (a species with osteocytic bones), SOST is expressed by a variety of nonosteocytic cells, none of which reside within the bone bulk. These findings argue that in fishes (and perhaps other vertebrates), nonosteocytic skeletal cells are both sensors and responders, shouldering duties believed exclusive to osteocytes. This previously unrecognized, SOST-dependent, osteocyte-independent mechanism challenges current paradigms of osteocyte exclusivity in bone-modeling regulation, suggesting the existence of multivariate feedback networks in bone modeling—perhaps also in mammalian bones—and thus arguing for the possibility of untapped potential for cell targets in bone therapeutics. Bone’s ability to change its morphology in response to load is widely attributed to osteocytes. A study of fish shows that bone can respond to load even in the absence of osteocytes, using a molecular mechanism that is conserved across vertebrates, albeit with different cellular effectors. Author summary Bone is a “smart” tissue, able to sense loads within its bulk and change its morphology when needed by a process named bone modeling. This process is carried out by bone-depositing cells (osteoblasts) and bone-resorbing cells (osteoclasts) and is regulated by osteocytes—cells that reside in small cavities within the bone tissue. Osteocytes are considered to function as mechanosensors, detecting areas of high loads that require modeling, and master regulators of osteoblasts and osteoclasts. Curiously, evolutionarily advanced fish do not have osteocytes in their bones, although more basal fish and all other bony vertebrates have them. In this paper, we show how the bones of advanced fish can respond to load in a mechanically efficient way despite the absence of osteocytes. We describe the molecular mechanism, which we found to be the same as in all other vertebrates; however, we show that the cellular effectors are different. The protein sclerostin, which is produced by osteocytes in mammals and is a potent suppressor of bone building by osteoblasts, is produced by a variety of nonosteocytic cells in medaka and zebrafish, and nonosteocytic skeletal cells serve as sensors and responders in these species. These results challenge current paradigms of osteocyte exclusivity in the regulation of bone modeling. |
| Databáze: | OpenAIRE |
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