Osteocytes but not osteoblasts directly build mineralized bone structures
| Autor: | Shuxian Lin, X. Baozhi Yuan, Yin Xiao, Zheng Wang, Xianglong Han, Yan Jing, Yinshi Ren, Bjorn R. Olsen, Minghao Zheng, Chi Ma, Jian Q. Feng, Ke Wang, Hu Zhao, Jun Wang, Lin Chen |
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| Rok vydání: | 2021 |
| Předmět: |
DMP1
Mineralization osteocyte Osteocytes Applied Microbiology and Biotechnology Bone and Bones Mice Calcification Physiologic Bone Density Bone cell medicine Animals Femur Wnt Signaling Pathway Molecular Biology beta Catenin Ecology Evolution Behavior and Systematics bone formation Mice Knockout Extracellular Matrix Proteins Osteomalacia Osteoblasts Tibia Phex Chemistry PHEX Age Factors Osteoblast Cell Biology medicine.disease PHEX Phosphate Regulating Neutral Endopeptidase Phenotype Cell biology Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Osteocyte osteoblast Familial Hypophosphatemic Rickets hypophosphatemia rickets Bone structure Research Paper Developmental Biology |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| DOI: | 10.7150/ijbs.61012 |
| Popis: | Bone-forming osteoblasts have been a cornerstone of bone biology for more than a century. Most research toward bone biology and bone diseases center on osteoblasts. Overlooked are the 90% of bone cells, called osteocytes. This study aims to test the hypothesis that osteocytes but not osteoblasts directly build mineralized bone structures, and that defects in osteocytes lead to the onset of hypophosphatemia rickets. The hypothesis was tested by developing and modifying multiple imaging techniques, including both in vivo and in vitro models plus two types of hypophosphatemia rickets models (Dmp1-null and Hyp, Phex mutation mice), and Dmp1-Cre induced high level of β-catenin models. Our key findings were that osteocytes (not osteoblasts) build bone similar to the construction of a high-rise building, with a wire mesh frame (i.e., osteocyte dendrites) and cement (mineral matrices secreted from osteocytes), which is a lengthy and slow process whose mineralization direction is from the inside toward the outside. When osteoblasts fail to differentiate into osteocytes but remain highly active in Dmp-1-null or Hyp mice, aberrant and poor bone mineralization occurs, caused by a sharp increase in Wnt-β-catenin signaling. Further, the constitutive expression of β-catenin in osteocytes recaptures a similar osteomalacia phenotype as shown in Dmp1 null or Hyp mice. Thus, we conclude that osteocytes directly build bone, and osteoblasts with a short life span serve as a precursor to osteocytes, which challenges the existing dogma. |
| Databáze: | OpenAIRE |
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