Parathyroid Hormone-Related Protein: An Essential Physiological Regulator of Adult Bone Mass

Endocrinology (Impact Factor: 4.5). 09/2004; 145(8):3551-3. DOI: 10.1210/en.2004-0509
Source: PubMed
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    • "PTHrP is a ubiquitously produced local paracrine, autocrine and intracrine factor, the role of which is to regulate cellular differentiation, proliferation, cell death, and epithelial calcium transport, both during development as well as in adult life [29]–[30]. Osteoblasts are also target cells for locally produced PTHrP and circulating PTH, as these cells express PTHR1 [31]–[33]. "
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    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.
    PLoS ONE 02/2014; 9(2):e88237. DOI:10.1371/journal.pone.0088237 · 3.23 Impact Factor
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    • "However, studies of PTHrP have mainly focused on bones and tumors. Experiments have demonstrated that PTHrP promotes bone formation and is an excellent osteogenic promoter that exerts rapid effects and few adverse reactions, even after years of clinical treatments for osteoporosis (OP) [2], [3], [4], [5]. Recently, PTHrP was reported to promote renal fibrogenesis, with the cooperation of TGF-β1 (transforming growth factor-β1), EGF (endothelial growth factor), and VEGF (vascular endothelial growth factor) [6]. "
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    ABSTRACT: After years of experiments and clinical studies, parathyroid hormone-related protein(PTHrP) has been shown to be a bone formation promoter that elicits rapid effects with limited adverse reaction. Recently, PTHrP was reported to promote fibrosis in rat kidney in conjunction with transforming growth factor-beta1 (TGF-β1), which is also a fibrosis promoter in liver. However, the effect of PTHrP in liver has not been determined. In this study, the promoting actions of PTHrP were first investigated in human normal hepatic stellate cells (HSC) and LX-2 cell lines. TGF-β1, alpha-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and collagen I mRNA were quantified by real-time polymerase chain reaction (PCR) after HSCs or LX-2 cells were treated with PTHrP(1-36) or TGF-β1. Protein levels were also assessed by western-blot analysis. Alpha-SMA were also detected by immunofluorescence, and TGF-β1 secretion was measured with enzyme-linked immunosorbent assay (ELISA) of HSC cell culture media. In cultured human HSCs, mRNA and protein levels of α-SMA, collagen I, MMP-2, and TGF-β1 were increased by PTHrP treatment. A similar increasing pattern was also observed in LX-2 cells. Moreover, PTHrP significantly increased TGF-β1 secretion in cultured media from HSCs. PTHrP activated HSCs and promoted the fibrosis process in LX-2 cells. These procedures were probably mediated via TGF-β1, highlighting the potential effects of PTHrP in the liver.
    PLoS ONE 10/2013; 8(10):e76517. DOI:10.1371/journal.pone.0076517 · 3.23 Impact Factor
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    • "Therefore, we suggest that serum PTHLH does not perfectly reflect secretion from the gastric mucosa, and that testing serum PTHLH in order to determine the ratio with gastrin levels in the gastric mucosa does not produce useful data. PTHLH selectively stimulates bone formation and has a rapid onset of action, and experimental and clinical research shows that even large doses are safe [13, 25–28]. "
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    ABSTRACT: Gastrectomy may disturb the body's mineral homeostasis, with osteopenia and osteoporosis being among the late outcomes. Parathyroid hormone-like hormone (PTHLH) was detected in rat gastric enterochromaffin-like (ECL) cells in 2005, and some researchers suggested that it was the hypothetical hormone gastrocalcin that is believed to lead to osteoporosis. Our objective was to learn whether PTHLH is expressed in human gastric ECL cells and to form a basic understanding about the relationship between PTHLH and gastrin. We collected normal human gastric mucosa specimens and serum samples from 28 patients. RT-PCR and immunohistochemical analysis demonstrated weak expression of PTHLH in ECL cells at the RNA and protein levels. A low level of PTHLH expression was also found in the serum. Serum gastrin did have a significant positive correlation with the relative ratio of PTHLH mRNA to β-actin levels in gastric mucosa (rs=0.569, p=0.002). This indicates that PTHLH has a low signal expression in human gastric ECL cells and that serum gastrin levels correlate with PTHLH RNA levels in gastric mucosa. Further work is needed to evaluate the functional role of PTHLH in ECL cells and to determine whether PTHLH is gastrocalcin.
    Digestive Diseases and Sciences 04/2011; 56(4):993-8. DOI:10.1007/s10620-010-1375-2 · 2.61 Impact Factor
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