Short carboxyl terminal parathyroid hormone peptides modulate human parathyroid hormone signaling in mouse osteoblasts

• Published in: Biochemical and biophysical research communications Vol. 572; pp. 15 - 19
• Main Authors: Kritmetapak, Kittrawee, Singh, Ravinder J., Craig, Theodore A., Hines, Jolaine M., Kumar, Rajiv
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2021
• Subjects: Alkaline phosphatase; cAMP; Carboxyl-terminal hPTH peptides; hPTH1-84; hPTH28-84; hPTH38-84; hPTH45-84; Mouse osteoblasts; Alkaline phosphatase; Carboxyl-terminal hPTH peptides; hPTH38-84; hPTH1-84; hPTH45-84; hPTH28-84; cAMP; Mouse osteoblasts
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.07.085

Novel human parathyroid hormone (hPTH) peptides of unknown biological activity have recently been identified in the serum of subjects with normal renal function, chronic renal failure, and end-stage renal disease through the application of liquid chromatography-high resolution mass spectrometry.
of experiments: To determine the bioactivity of these peptides, we synthesized hPTH28-84, hPTH38-84, and hPTH45-84 peptides by solid phase peptide synthesis and tested their bioactivity in MC3T3-E1 mouse osteoblasts, either individually or together with the native hormone, hPTH1-84, by assessing the accumulation of 3´,5´-cyclic adenosine monophosphate (cAMP) and the induction of alkaline phosphatase activity.
Increasing doses of hPTH1-84 (1–100 nM) increased the accumulation of cAMP and alkaline phosphatase activity in osteoblasts. hPTH28-84, hPTH38-84, and hPTH45-84 in concentrations of 1–100 nM were biologically inert. Surprisingly, 100 nM hPTH38-84 and hPTH45-84 increased the accumulation of cAMP in osteoblasts treated with increasing amounts of hPTH1-84. Human PTH28-84 had no effects on cAMP activity alone or in combination with hPTH1-84. Conversely, 100 nM hPTH38-84, hPTH45-84, and hPTH28-84 blocked the activation of alkaline phosphatase activity by hPTH1-84.
The data show that the short carboxyl-terminal hPTH peptides, hPTH38-84 and hPTH45-84, increase the amount of cellular cAMP generated in cultured osteoblasts in response to treatment with full-length hPTH1-84 when compared to full-length hPTH1-84 alone. Human PTH28-84 had no effect on cAMP activity alone or in combination with hPTH1-84. Human PTH28-84, hPTH38-84 and hPTH45-84 reduced the effects of hPTH1-84 in osteoblasts with respect to the induction of alkaline phosphatase activity compared to hPTH1-84 alone. Short carboxyl peptides of human PTH are biologically inert but when administered together with full-length hPTH1-84 modulate the bioactivity of hPTH1-84 in osteoblasts.
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•Human PTH38-84 and 45–84 enhance hPTH1-84-mediated osteoblast cAMP accumulation.•PTH28-84, 38–84 and 45–84 reduce hPTH1-84-mediated osteoblast alkaline phosphatase.•PTH28-84, 38–84, and 45–84 do not alter osteoblast cAMP or alkaline phosphatase.•Short carboxyl terminal PTH peptides might modulate PTH1-84 activity in osteoblasts.