Effects on Bone In Vitro of Bovine Parathyroid Hormone and Synthetic Fragments Representing Residues 1–34, 2–34 and 3–34

Abstract

The biological activities of bovine parathyroid hormone (BPTH) and fragments comprising portions of its amino-terminal sequence have been compared in three different assay systems using embryonic rat bone in vitro. Whereas the 3-34 fragment was without significant activity the 1-34 fragment caused all the actions characteristic of BPTH 1-84, extending to bone previous evidence that the amino-terminal residues are sufficient for expression of the biological effects of intact parathyroid hormone. However, the relative potencies of the fragment and the intact hormone were different in the various systems. BPTH 1-34 showed relatively low osteolytic activity and induced anabolic effects in both osteoblasts and cartilage cells of cultivated embryonic mouse radii which were not evoked by the intact hormone. Further work is required to determine the mechanisms responsible for these interesting alterations in relative potency of fragment and native hormone.

Parathyroid Hormone and Parathyroid Hormone-related Protein Exert Both Pro- and Anti-apoptotic Effects in Mesenchymal Cells

“…Our data suggest that functional PTH receptors, likely through affecting proliferation or apoptosis, contribute to the increase of mesenchymal cell numbers. These results agree with studies reporting that PTH stimulates osteoblast proliferation (2,4) and increases osteoblast number (44) and that a constitutively active PTH-1R increases osteoblast number in trabecular bone in transgenic mice (15). Additionally, Watson et al (45) suggest that the PTH-1R localizes to the nucleus and may be associated with ligand-independent proliferation.…”

Comparison of the effects of a potent synthetic analog of bovine parathyroid hormone with native bPTH-(1-84) and synthetic bPTH-(1-34) on bone resorption and collagen synthesis

“…No qualitative differences in the response to any of the three bPTH compounds were observed. Although it has previously been suggested that bPTH-(1-34) was a slower stimulator of bone resorption than bPTH-(I-84) and was able to enhance rather than inhibit bone formation [3][4][5], we were unable to confirm the presence of these biological proper- ties. However, our studies were carried out in quite different culture systems.…”

“…The analog Nle-8, Nle-18, Tyr-34 bPTH-(1-34) amide (PTH-Ana) was found to be approximately 2 times as potent as the unsubstituted bPTH-(1-34) in a renal adenylate cyclase assay [2], whereas bPTH-(I-34) and the native hormone bPTH-(1-84) are equipotent on a molar basis in this assay. Differences in biological properties between the sequence 1-34 and 1-84 of bPTH have been described in bone culture systems [3][4][5], but PTH-Ana has not been tested on bone in vitro. The present study compares PTH-Ana with bPTH-(1-84) and bPTH-(I-34) using systems [6,7] in which PTH had been shown previously to stimulate bone resorption and inhibit bone collagen synthesis.…”

Backbone-methylated Analogues of the Principle Receptor Binding Region of Human Parathyroid Hormone

“…PTH and its paracrine equivalent, parathyroid hormone-related peptide (PTHrP), bind to a G-protein-linked seven-transmembrane receptor (P1R) (6) and activate both adenylyl cyclase (AC)/cAMP-dependent protein kinase and phospholipase-C (PLC)-dependent and -independent protein kinase C pathways (7,8). Deletion of even two N-terminal residues leads to a total loss of AC and PLC signaling, as well as the anabolic activities (9). In contrast, the PLC-independent protein kinase C activity requires the C-terminal region of hPTH (1-34) (10,11).…”