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Mechanical responses and signal transduction pathways in stretched osteocytes
1Kanagawa Dental College, Department of Oral Biochemistry, Yokosuka, Japan.
Journal of Bone and Mineral Metabolism
|March 20, 1999
Summary
Osteocytes respond to mechanical strain through complex signaling pathways involving prostaglandin G/H synthase-2 (PGHS-2) and calcium influxes, crucial for bone
Area of Science:
- Bone biology and mechanotransduction.
- Cellular signaling pathways in osteocytes.
- Molecular mechanisms of bone anabolism.
Background:
- Osteocytes, resident bone cells, are thought to sense mechanical loading and initiate anabolic responses.
- The precise stimuli and signal transduction pathways osteocytes use remain largely unknown.
- Mechanical loading influences bone through modulators like parathyroid hormone (PTH) and prostanoids.
Purpose of the Study:
- To investigate the specific stimuli and signaling pathways osteocytes employ to respond to mechanical strain.
- To elucidate the role of prostaglandin G/H synthase-2 (PGHS-2) and calcium in osteocyte mechanotransduction.
- To understand the molecular basis of the bone's "memory effect" to mechanical stimulation.
Main Methods:
- Culturing primary rat bone cells at different developmental stages.
- Applying physiological levels of mechanical stretching to cultured osteocytes.
- Measuring cellular responses including cAMP secretion, protein production (IGF-I, osteocalcin), and mRNA expression (c-fos, PGHS-2).
- Utilizing inhibitors like NS398, gadolinium (Gd3+), and benzamil to block specific signaling components.
Main Results:
- Young osteocytes show distinct responses to strain, including early cAMP secretion and later IGF-I and osteocalcin production.
- PGHS-2 gene expression exhibits a distinct biphasic pattern, with a significant peak around 8 hours post-stretching.
- Osteocalcin and IGF-I expression are dependent on PGHS-2 activity, and extracellular calcium is essential for the response to stretching.
- Blockers of stretch-activated and epithelial-like Na channels significantly inhibit osteocalcin expression, suggesting a role for these channels and calcium influx.
Conclusions:
- PGHS-2 plays a critical role in the prolonged anabolic responses of osteocytes to mechanical stimulation, contributing to bone's "memory effect".
- Extracellular calcium and specific ion channels (stretch-activated and Na+ channels) are essential for osteocyte mechanotransduction.
- Calcium influxes, potentially through Ser/Thr kinase signaling pathways, are likely triggers for the anabolic response of bone to mechanical stretching.