Parathyroid hormone-lymphocyte interactions modulate bone resorption.
The biologically active PTH fragment 1-34 induces mononuclear leukocytes to produce a substance(s) capable of increasing bone resorption, as assayed in an organ culture system. The onset of the effect is evident at 2 days and lasts at least 7 days. The cell responsible for this effect appears to be an activated nonadherent lymphocyte (probably T-cell). PTH-(1-34) induces these cells to secrete this factor(s). The presence of adherent mononuclear leukocytes or appropriate conditioned medium appears to augment this response. Secretion of this factor(s) is specific for PTH-(1-34); it is not induced by biologically inactive PTH fragments, nor can it be induced by incubating mononuclear leukocytes with other hormones, including human PRL or lysine vasopressin. On the other hand, PTH-(1-34), human PRL, and lysine vasopressin all activate mononuclear leukocytes, as determined by [3H]thymidine incorporation. Biologically inactive PTH fragments do not. Thus, while lymphocyte activation may be a necessary prerequisite to lymphocyte modulation of bone resorption, it is not sufficient of itself. The PTH fragment 1-34 activates mononuclear leukocytes and specifically induces nonadherent lymphocytes to produce a substance(s) capable of increasing bone resorption. Preliminary characterization of this substance(s) shows that cellular components of the organ culture are necessary to demonstrate the increased resorptive capacity of PTH-stimulated lymphocyte supernatants. Secondly, this resorptive capacity is heat sensitive. Finally, this substance(s) appears to have a nominal molecular radius greater than 14,000 daltons, but less than 50,000 daltons.
D001862:Bone Resorption; D002448:Cell Adhesion; D003470:Culture Media; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology*; D008970:Molecular Weight; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D019379:Teriparatide; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D003470:Culture Media; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D013936:Thymidine; D007213:Indomethacin