Abstract
The controversy exists about the biological activity of carboxyl (C)-terminal parathyroid hormone (PTH) fragments. The present study was performed to examine the effect of C-terminal PTH fragments on osteoclast-like cell formation and bone-resorbing activity. Human (h) PTH-(1-84) caused a stimulation of osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures more effectively than hPTH-(1-34). All of the C-terminal fragments examined [hPTH-(35-84), hPTH-(53-84) and hPTH-(69-84)] significantly stimulated osteoclast-like cell formation. The conditioned medium from osteoblastic UMR-106 cells pretreated with C-terminal PTH as well as amino-terminal PTH significantly stimulated osteoclast-like cell formation from mouse hemopoietic blast cells supported by granulocyte-macrophage colony stimulating factor. Moreover, all of the C-terminal fragments also caused a stimulation of osteoclast-like cell formation from hemopoietic blast cells even in the absence of osteoblasts. As for bone-resorbing activity of mature osteoclasts, all of the C-terminal fragments stimulated bone-resorbing activity in osteoblast-containing mouse bone cell cultures, while these fragments did not affect bone-resorbing activity of isolated rabbit osteoclasts. The present study indicates that C-terminal PTH fragments stimulate osteoclast-like cell formation as well as bone-resorbing activity of mature osteoclasts in the presence of osteoblast and also accelerate osteoclast-like cell formation from hemopoietic blast cells in the absence of osteoblasts.
Similar content being viewed by others
References
Potts JT Jr, Tregear GW, Keutmann HT et al.: Synthesis of a biologically active N-terminal tetratriacontapeptide of parathyroid hormone. Proc Nat Acad Sci USA 68: 63–67, 1971
Juppner H, Abou-Samra AB, Freeman MW et al.: A G protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science 254: 1024–1026, 1991
Abou-Samra AB, Juppner H, Force T et al.: Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: A single receptor stimulates intracellular accumulation of both cAMP and inositol triphosphates and increases intracellular free calcium. Proc Natl Acad Sci USA 89: 2732–2736, 1992
Civitelli R, Reid IR, Westbrook S et al.: PTH elevates inositol polyphosphates and diacylglycerol in a rat osteoblast-like cell line. Am J Physiol 255: E660-E667, 1988
Reid IR, Civitelli R, Halstead LR et al.: Parathyroid hormone acutely elevates intracellular calcium in osteoblastlike cells. Am J Physiol 252: E45-E51, 1987
Kano J, Sugimoto T, Fukase M et al.: The activation of cAMP-dependent protein kinase is directly linked to the regulation of osteoblast proliferation (UMR-106) by parathyroid hormone. Biochem Biophys Res Commun 177: 365–369, 1991
Kano J, Sugimoto T, Fukase M et al.: The direct involvement of cAMP-dependent protein kinase in the regulation of collagen synthesis by parathyroid hormone (PTH) and PTH-related peptide in osteoblast-like osteosarcoma cells (UMR-106). Biochem Biophys Res Commun 184: 525–529, 1992
Sugimoto T, Kano J, Fukase M et al.: Second messenger signaling in the regulation of cytosolic pH and DNA synthesis by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic osteosarcoma cells: role of Na+/H+ exchange. J Cell Physiol 152: 28–34, 1992
Kaji H, Sugimoto T, Kanatani M et al.: The activation of cAMP-dependent protein kinase is directly liked to the stimulation of bone resorption by parathyroid hormone. Biochem Biophys Res Commun 182: 1356–1361, 1992
Kaji H, Sugimoto T, Fukase M et al.: Role of dual signal transduction systems in the stimulation of bone resorption by parathyroid hormone-related peptide: the direct involvement of cAMP-dependent protein kinase. Horm Metab Res 25: 421–424, 1993
Ikeda K, Sugimoto T, Fukase M et al.: Protein kinase C is involved in PTH-induced homologous desensitization by directly affecting PTH receptor in the osteoblastic osteosarcoma cells. Endocrinology 128: 2901–2906, 1991
Hruska KA, Blondin J, Bass R et al.: Effect of intact parathyroid hormone on hepatic glucose release in the dog. Clin Invest 64: 1016–1023, 1979
El-Shahawy MA, Fadda GZ, Wisner JR Jr et al.: Acuts administration of intact parathyroid hormone but not its amino-terminal fragment stimulates volume of pancreatic secretion. Nephron 57: 69–74, 1991
Doherty CC, LaBelle P, Collins JF et al.: Effect of parathyroid hormone on random migration of human polymorphonuclear leukocytes. Am J Nephrol 8: 212–219, 1988
Mckee MD, Murray TM: Binding of intact parathyroid hormone to chicken renal plasma membranes: evidence for a second binding site with carboxyl-terminal specificity. Endocrinology 117: 1930–1939, 1985
Rao LG, Murray TM: Binding of intact parathyroid hormone to rat osteosarcoma cells: major contribution of binding sites for the carboxyl-terminal region of the hormone. Endocrinology 117: 1632–1638, 1985
Murray TM, Rao LG, Muzaffar SA et al.: Human parathyroid hormone carboxyterminal peptide (53–84) stimulates alkaline phosphatase activity in dexamethasone-treated rat osteosarcoma cells in vitro. Endocrinology 124: 1097–1099, 1989
Kaji H, Sugimoto T, Kanatani M et al.: Carboxyl-terminal parathyroid hormone fragments stimulate osteoclast-like formation and osteoclastic activity. Endocriniology 134: 1897–1904, 1994
Udagawa N, Takahashi N, Akatsu T et al.: Origin of osteoclasts: Mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci USA 87: 7260–7264, 1990
Hakeda Y, Hiura K, Sato T et al.: Existence of parathyroid hormone binding sites on murine hemopoietic blast cells. Biochem Biophys Res Commun 163: 1481–1486, 1989
Sugimoto T, Kanatani M, Kaji H et al.: Second messenger signaling of PTH- and PTH-related peptide-stimulated osteoclast-like cell formation from mouse hemopoietic blast cell: role of cAMP-dependent protein kinase and protein kinase C. Am J Physiol 265: E367-E373, 1993
Author information
Authors and Affiliations
About this article
Cite this article
Kaji, H., Sugimoto, T., Kanatani, M. et al. Stimulatory effect of carboxyl-terminal parathyroid hormone fragments on osteoclast-like cell formation and osteoclastic activity. J Bone Miner Metab 12 (Suppl 1), S125–S129 (1994). https://doi.org/10.1007/BF02375689
Issue Date:
DOI: https://doi.org/10.1007/BF02375689