Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk
| Autor: | Weiguo Zou, Sutada Lotinun, Nan Wu, Xiuling You, Lijun Wang, Lingli Zhang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Science Cellular differentiation Bone pathology General Physics and Astronomy Osteoclasts General Biochemistry Genetics and Molecular Biology Bone resorption Collagen Type IX Ion Channels Article Bone remodeling 03 medical and health sciences Mechanostat Fractures Bone 0302 clinical medicine Bone remodelling Osteoclast medicine Animals Homeostasis Bone Resorption lcsh:Science Collagen Type II Mice Knockout Multidisciplinary Osteoblasts Chemistry Osteoblast Cell Differentiation General Chemistry Cell biology Bone quality and biomechanics Crosstalk (biology) 030104 developmental biology medicine.anatomical_structure Hindlimb Suspension 030220 oncology & carcinogenesis Osteoporosis lcsh:Q Female Stress Mechanical |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2041-1723 |
| Popis: | Wolff’s law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict the existence of a mechanostat that links strain induced by mechanical forces to skeletal remodeling. However, how the mechanostat influences bone remodeling remains elusive. Here, we find that Piezo1 deficiency in osteoblastic cells leads to loss of bone mass and spontaneous fractures with increased bone resorption. Furthermore, Piezo1-deficient mice are resistant to further bone loss and bone resorption induced by hind limb unloading, demonstrating that PIEZO1 can affect osteoblast-osteoclast crosstalk in response to mechanical forces. At the mechanistic level, in response to mechanical loads, PIEZO1 in osteoblastic cells controls the YAP-dependent expression of type II and IX collagens. In turn, these collagen isoforms regulate osteoclast differentiation. Taken together, our data identify PIEZO1 as the major skeletal mechanosensor that tunes bone homeostasis. Mechanical forces induce bone remodeling, but how bone cells sense mechanical signaling is unclear. Here, the authors show that loss of the mechanotransduction channel Piezo1 in osteoblastic cells impairs osteoclast activity via YAP signaling and collagen expression, leading to reduced bone mass and spontaneous fractures. |
| Databáze: | OpenAIRE |
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