Recombinant human parathyroid hormone related protein 1-34 and 1-84 and their roles in osteoporosis treatment.

Abstract

Osteoporosis is a common disorder characterized by compromised bone strength that predisposes patients to increased fracture risk. Parathyroid hormone related protein (PTHrP) is one of the candidates for clinical osteoporosis treatment. In this study, GST Gene Fusion System was used to express recombinant human PTHrP (hPTHrP) 1-34 and 1-84. To determine whether the recombinant hPTHrP1-34 and 1-84 can enhance renal calcium reabsorption and promote bone formation, we examined effects of recombinant hPTHrP1-34 and 1-84 on osteogenic lineage commitment in a primary bone marrow cell culture system and on osteoporosis treatment. Results revealed that both of recombinant hPTHrP1-34 and 1-84 increased colony formation and osteogenic cell differentiation and mineralization in vitro; however, the effect of recombinant hPTHrP1-84 is a little stronger than that of hPTHrP1-34. Next, ovariectomy was used to construct osteoporosis animal model (OVX) to test activities of these two recombinants in vivo. HPTHrP1-84 administration elevated serum calcium by up-regulating the expression of renal calcium transporters, which resulted in stimulation of osteoblastic bone formation. These factors contributed to augmented bone mass in hPTHrP1-84 treated OVX mice but did not affect bone resorption. There was no obvious bone mass alteration in hPTHrP1-34 treated OVX mice, which may be, at least partly, associated with shorter half-life of hPTHrP1-34 compared to hPTHrP1-84 in vivo. This study implies that recombinant hPTHrP1-84 is more effective than hPTHrP1-34 to enhance renal calcium reabsorption and to stimulate bone formation in vivo.

• Authors: Hua Wang, Jingning Liu, Ying Yin, Jun Wu, Zilu Wang, Dengshun Miao, Wen Sun
• Journal: PloS one (PLoS One) Vol. 9 Issue 2 Pg. e88237 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24516619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Transport Proteins
• Parathyroid Hormone-Related Protein
• Peptide Fragments
• Recombinant Proteins
• parathyroid hormone-related protein (1-34)
• parathyroid hormone-related protein (1-84)
• Calcium

Topics

• Animals
• Bone Marrow Cells (drug effects, metabolism, pathology)
• Bone Resorption (blood, complications, drug therapy, pathology)
• Calcium (metabolism)
• Cell Lineage (drug effects)
• Female
• Half-Life
• Humans
• Kidney (drug effects, metabolism, pathology)
• Male
• Membrane Transport Proteins (metabolism)
• Mice, Inbred C57BL
• Organ Size (drug effects)
• Osteoblasts (drug effects, metabolism, pathology)
• Osteoclasts (drug effects, metabolism, pathology)
• Osteogenesis (drug effects)
• Osteoporosis (blood, drug therapy, pathology)
• Parathyroid Hormone-Related Protein (isolation & purification, therapeutic use)
• Peptide Fragments (isolation & purification, therapeutic use)
• Rats, Wistar
• Recombinant Proteins (therapeutic use)
• Stem Cells (cytology, drug effects)