Role of Dual Signal Transduction Systems in the Stimulation of Bone Resorption by Parathyroid Hormone-Related Peptide

Summary

The present study was performed to compare the effect of parathyroid hormone-related peptide (PTHrP) on bone resorption with that of parathyroid hormone (PTH) and clarify the participation of PTHrP-responsive dual signal transduction systems involving cAMP-dependent protein kinase (PKA) and calcium/protein kinase C (Ca/PKC) in the stimulation of bone resorption by PTHrP. Bone resorbing activity was estimated as the number of pits formed on the dentine slice and total area of pits per slice in bone cells derived from 2 week-old mice. Human (h)PTHrP-(1-34) (10⁷M) did. The stimulated bone resorption as potent as hPTH-(1-34) (10⁷M) did. The stimulation of bone resorption by hPTHrP-(1-34) and hPTH-(1-34) was equally blocked by either simultaneous treatment with 10^-8 M eel calcitonin or pretreatment with 10^-7M [Nle^8,18Tyr³⁴]hPTH-(3-34)amide. Rp-cAMPS, an antagonist in the activation of PKA, equally attenuated bone resorption stimulated by PTHrP as well as by PTH. A23187 (10^-7 M) caused a significant stimulation of bone resorption. These findings indicate the direct involvement of PKA activation and a contributory role of an increase in cytosolic calcium in the stimulation of bone resorption by PTHrP and suggest that PTHrP stimulates bone resorption presumably through the same mechanism as PTH does.

Key words

Parathyroid Hormone-Related Peptide - Bone Resorption - cAMP-Dependent Protein Kinase