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Nck1 deficiency accelerates unloading-induced bone loss
- Source :
- Journal of Cellular Physiology. 228:1397-1403
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- Mechanical stress is an important signal to determine the levels of bone mass. Unloading-induced osteoporosis is a critical issue in bed-ridden patients and astronauts. Many molecules have been suggested to be involved in sensing mechanical stress in bone, though the mechanisms involved in this phenomenon are not fully understood. Nck1 is an adaptor protein known to mediate signaling from plasma membrane-activated receptors to cytosolic effectors regulating actin cytoskeleton remodeling. Nck1 has also been implicated in cellular responses to endoplasmic reticulum stress. In vitro, in case of cell stress the actin cytoskeleton is disrupted and in such cases Nck1 has been reported to enter the nucleus of the cells to mediate the nuclear actin polymerization. However, the role of Nck1 in vivo during the bone response to mechanical stimuli is unknown. The purpose of this study is to examine the role of Nck1 in unloading-induced bone loss in vivo. Sciatic and femoral nerve resection was conducted. Neurectomy-based unloading enhanced Nck1 gene expression in bone about twofold. Using the Nck1 deficient mice and control Nck1+/+, effects of neurectomy-based unloading on bone structure were examined. Unloading reduced bone volume in wild type mice by 30% whereas the levels in bone loss were exacerbated to 50% in Nck1 deficient mice due to neurectomy after 4 weeks. These data demonstrate that Nck1 gene deficiency accelerates the mechanical unloading-induced bone loss suggesting Nck1 to be a crucial molecule in mechanical stress mediated regulation in bone metabolism.
- Subjects :
- Male
Physiology
Clinical Biochemistry
Osteoporosis
Gene Expression
Bone remodeling
Mice
medicine
Animals
Humans
Bone Resorption
Muscle, Skeletal
Receptor
Actin
Adaptor Proteins, Signal Transducing
Cell Nucleus
Mice, Knockout
Oncogene Proteins
Denervation
Osteoblasts
Chemistry
Endoplasmic reticulum
Signal transducing adaptor protein
3T3 Cells
Cell Biology
Actin cytoskeleton
medicine.disease
Sciatic Nerve
Actins
Biomechanical Phenomena
Cell biology
Muscular Atrophy
Hindlimb Suspension
Immunology
Femoral Nerve
Locomotion
Subjects
Details
- ISSN :
- 00219541
- Volume :
- 228
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi.dedup.....119ce32971c94f2af64975cf0acb86f6
- Full Text :
- https://doi.org/10.1002/jcp.24317