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Stretch-induced PTH-related protein gene expression in osteoblasts
Xuesong Chen1, Carolyn M Macica, Kong Wah Ng
1Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-2080, USA.
Summary
Mechanical force stimulates bone growth by inducing parathyroid hormone-related protein (PTHrP) via TREK-2 potassium channels in bone cells. This suggests PTHrP mediates bone
Area of Science:
- Biochemistry
- Cell Biology
- Bone Biology
Background:
- Mechanical force is known to have anabolic effects on bone tissue.
- Parathyroid hormone-related protein (PTHrP) is mechanically inducible in smooth muscle cells and has anabolic effects on bone.
Purpose of the Study:
- To investigate whether PTHrP mediates the anabolic effects of mechanical force on bone.
- To explore the role of TREK-2 stretch-activated potassium channels in mechanical induction of PTHrP.
Main Methods:
- Osteoblast-like cells (UMR201-10B) were subjected to mechanical loading via hypotonic swelling and cyclical stretch.
- PTHrP gene expression was quantified using RNase protection assay and real-time quantitative PCR.
- TREK-2 channels were identified by PCR, and their role was assessed using siRNA and intracellular acidification.
Main Results:
- Mechanical stretching rapidly increased PTHrP mRNA in osteoblast-like cells.
- TREK-2 potassium channels were identified in osteoblast-like cells.
- siRNA targeting TREK-2 reduced PTHrP mRNA induction, and intracellular acidification also increased PTHrP mRNA.
Conclusions:
- PTHrP is rapidly induced by mechanical stretching in osteoblast-like cells.
- TREK-2 potassium channels are involved in the mechanical induction of PTHrP in bone cells.
- PTHrP is a potential endogenous mediator of the bone-anabolic effects of mechanical force.