Expression of parathyroid hormone-related protein in cells of osteoblast lineage

Suda, Naoto; Gulespie, Matthew T.; Traianedes, Kathy; Zhou, Hong; Ho, Patricia W. M.; Hards, D.K.; Allan, Elizabeth; Martin, T. J.; Moseley, Jane M.

doi:10.1002/(sici)1097-4652(199601)166:1<94::aid-jcp11>3.0.co;2-p

Cited by 104 publications

(62 citation statements)

References 47 publications

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“…The expression of PTHrP has been investigated in cultures of cells of osteohlastic lineage [33]. In cultures of calvarial cells obtained by sequential digestion with collagenase, the expression of PTHrP mRNA is reported to be increased in less differentiated populations and reduced in mature osteoblast-rich populations.…”

Section: Discussionmentioning

confidence: 99%

“…During embryonal cartilage development, PTHrP is expressed in the perichondrium induced by Indian hedgehog (Ihh), and regulates the rate of chondrocyte differentiation [38]. PTHrP is also expressed by various osteoblastic cells including an osteosarcoma cell line (UMR 106), preosteoblastic cell line ( U M R 201), primary rat calvarial Cells and primary human osteoblastic cells, as well as 512 ' Orthopueriic Reseurclz 21 (2003) [511][512][513][514][515][516][517][518][519][520] in cultured rat calvariae [33]. The N-terminal PTHrP region has some influence on cell proliferation, DNA synthesis, alkaline phosphatase (ALP) activity and collagen synthesis in osteoblastic cells [9,10,18,19,35].…”

Section: Introductionmentioning

confidence: 99%

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Expression of parathyroid hormone‐related peptide and insulin‐like growth factor I during rat fracture healing

Okazaki

Jingushi

Ikenoue

et al. 2003

Journal Orthopaedic Research

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Parathyroid hormone-related peptide (PTHrP) and insulin-like growth factor I (IGF-I) are both involved in the regulation of bone and cartilage metabolisms and their interaction has been reported in osteoblasts. To investigate the interaction of PTHrP and IGF-I during fracture healing, the expression of mRNA for PTHrP and IGF-I, and receptors for PTHlPTHrP and IGF were examined during rat femoral fracture healing using an in situ hybridization method and an immunohistochemistry method, respectively. During intramembranous ossification, PTHrP mRNA, IGF-I mRNA and IGF receptors were detected in preosteoblasts, differentiated osteoblasts and osteocytes in the newly formed trabecular bone. PTHlPTHrP receptors were markedly detected in osteoblasts and osteocytes, but only barely so in preosteoblasts. During cartilaginous callus formation, PTHrP mRNA was expressed by mesenchymal cells and proliferating chondrocytes. PTHlPTHrP receptors were detected in proliferating chondrocytes and early hypertrophic chondrocytes. IGF-I mRNA and IGF receptor were co-expressed by mesenchymal cells, proliferating chondrocytes, and early hypertrophic chondrocytes. At the endochondral ossification front, osteoblasts were positive for PTHrP and IGF-I mRNA as well as their receptors. These results suggest that IGF-I is involved in cell proliferation or differentiation in mesenchymal cells, periosteal cells, osteoblasts and chondrocytes in an autocrine andlor paracrine fashion. Furthermore, PTHrP may be involved in primary callus formation presumably co-operating with IGF-I in osteoblasts and osteocytes, and by regulating chondrocyte differentiation in endochondral ossification. IntroductionDuring fracture healing, several cellular events occur simultaneously and/or sequentially: inflammatory reaction, chondrogenesis, intramembranous ossification and endochondral ossification, resulting in the formation of a fracture callus followed by bony union. These dynamic events of bone metabolism are biologically regulated and can be investigated representatively in animal fracture models [15]. It has been reported that various local regulators such as cytokines and growth factors are expressed during fracture healing suggesting they regulate proliferation and/or differentiation of cells involved in fracture healing [11,39]. Since many growth factors regulate biological reaction of cells in co-operation with other factors or modulate the function of other factors [9,10,36], these interaction between different local regulators may be important for the well-organized repair process of fracture healing.Parathyroid hormone-related peptide (PTHrP) was originally isolated from tumors associated with humoral hypercalcemia of malignancy [34]. It has been reported that PTHrP is expressed in a wide variety of fetal and neonatal tissues [8,37], and acts in an autocrine/paracrine fashion binding with the same receptor as parathyroid hormone (PTH) does [16]. During embryonal cartilage development, PTHrP is expressed in the perichondrium induced by Indian ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of parathyroid hormone‐related peptide and insulin‐like growth factor I during rat fracture healing

Okazaki

Jingushi

Ikenoue

et al. 2003

Journal Orthopaedic Research

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“…As shown in Fig. 1C, when determined by RT-PCR at cycles before reaching plateau (30), PTHrP and FGFR3, two important molecules regulating chondrocyte proliferation and …”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr) Formentioning

confidence: 84%

“…Amplification was performed by denaturation at 94°C for 1 min, annealing at 55°C for 1 min, and extension at 72°C for 1 min using GeneAmp PCR System 9700 (Applied Biosystem Japan Ltd, Tokyo, Japan). The expression of PTHrP and FGFR3 was examined at amplification cycles that do not reach the plateau for PCR reaction (30). Primer construction: rat/mouse PTHrP: sense 5'-TGGTGTTCCTGCTCAGCTA-3', antisense 5'-CCTCGTCGTCTGACCCAAA-3 (38), rat/mouse FGFR3: sense 5'-AGAAGGCTGCTTTG GACA-3', antisense 5'-TGAGCTGTTCCTCTGG CA-3' (16), rat/mouse GAPDH; sense 5'-CATGG AGAAGGCTGGGGCTC-3', antisense 5'-AACGG ATACATTGGGGGTAG-3' (33).…”

Section: Methodsmentioning

confidence: 99%

Histological assessments on the abnormalities of mouse epiphyseal chondrocytes with short term centrifugal loading

et al. 2007

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We have examined the morphological changes in chondrocytes after exposure to experimental hypergravity. Tibial epiphyseal cartilages of 17-days-old mouse fetuses were exposed to centrifugation at 3G for 16 h mimicking hypergravitational environment (experimental group), or subjected to stationary cultures (control group). Centrifugation did not affect the sizes of epiphyseal cartilage, chondrocyte proliferation, type X collagen-positive hypertrophic zone, and the mRNA expressions of parathyroid hormone-related peptide and fibroblast growth factor receptor III. However, centrifuged chondrocytes showed abnormal morphology and aberrant spatial arrangements, resulting in disrupted chondrocytic columns. Through histochemical assessments, actin filaments were shown to distribute evenly along cell membranes of control proliferative chondrocytes, while chondrocytes subjected to centrifugal force developed a thicker layer of actin filaments. Transmission electron microscopic observations revealed spotty electron-dense materials underlying control chondrocytes' cell membranes, while experimental chondrocytes showed their thick layer. In the intracolumnar regions of the control cartilage, longitudinal electron-dense fibrils were associated with short cytoplasmic processes of normal chondrocytes, indicating assumed cell-tomatrix interactions. These extracellular fibrils were disrupted in the centrifuged samples. Summarizing, altered actin filaments associated with cell membranes, irregular cell shape and disappearance of intracolumnar extracellular fibrils suggest that hypergravity disturbs cell-to-matrix interactions in our cartilage model.The unique mechanical properties of the cartilage are conferred by its avascular composition and the complexity of its extracellular matrices including collagen fibrils, aggrecan, link proteins and so forth. Mesenchymal condensation, chondrocytic differentiation and subsequent matrix synthesis are genetically programmed, and regulated by microenvironmental influences such as soluble mediators, e.g., parathyroid hormone-related peptide (PTHrP) and fibroblast growth factor receptor III (FGFR3) (1, 2, 14). Currently, however, many investigators are paying attention to the fundamental role played by mechanical loading in chondrocyte regulation and cartilage dysfunction. Gravity, the force of attraction between all masses in the universe, can be understood as a source of loading upon chondrocytes and their surroundings. Altered gravity has been shown to affect

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“…(24,25) This includes bone, where it is produced by cells within the osteoblast lineage. (26)(27)(28)(29) PTHrP homology with PTH is restricted to the amino-terminal region, equipping them to act with equivalent potencies on the common receptor, PTHR1. (30,31) PTHrP has other actions mediated by unique regions within the molecule beyond the amino-terminal region that is homologous with PTH.…”

Section: Anabolic Therapy With Parathyroid Hormone (Pth) and Abaloparmentioning

confidence: 99%

Abaloparatide Is an Anabolic, but Does It Spare Resorption?

Martın

Seeman

2016

Journal of Bone and Mineral Research

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L ongevity is increasing the burden of fractures. Although antiresorptive therapy slows remodeling, it does not prevent or repair microstructural deterioration. The challenge is to reconstruct the skeleton. The more advanced the patient's age, the more likely that microstructural deterioration is severe and so the more rational the choice of an anabolic agent as first-line therapy. PTH(1-34) (teriparatide) reduces vertebral and nonvertebral fracture risk, in part, by increasing bone matrix volume. Abaloparatide has also recently been reported to reduce morphometric vertebral fracture risk (1,2) and is thus a most welcome addition to the therapeutics of bone fragility. Abaloparatide is claimed to produce its anabolic effect with a much lesser effect on bone resorption than occurs with teriparatide. In this Commentary, we query the latter proposition, which we suggest contains two misconceptions: first, that with teriparatide treatment an anabolic window exists during which bone formation predominates but then is offset by bone resorption, which follows later, and second that less bone resorption occurs with abaloparatide, leaving the "window" open longer and allowing more bone formation. Anabolic Therapy With Parathyroid Hormone (PTH) and AbaloparatideTo understand the fallacies in these two notions, the mythical anabolic window and the purported lesser resorptive effect of abaloparatide, it is necessary first to discuss the mechanisms of action of PTH. The idea that intermittent injection of PTH might promote bone formation was proposed more than 80 years ago by Albright (3) and shown in rats by Selye.Progress was slow, with no attempt to study PTH treatment clinically until the 1970s. The first clinical trial was published in 2001 (5) and was stopped after 18 months because of a toxicity study that showed dose-dependent development of osteosarcoma in rats treated throughout their lives. (6) With the total number of subjects in the clinical trial reduced to 1600 and the duration of treatment being only 18 months, no potential antihip fracture efficacy could be demonstrated, but vertebral and nonvertebral fracture risk was reduced and bone mineral density (BMD) increased.The efficacy of teriparatide as an anabolic therapy depends on intermittent injections, each achieving a sharp peak of PTH in the blood.(7) When teriparatide therapy is begun, circulating bone formation markers increase rapidly, with a delayed appearance of resorption markers, giving rise to the concept of the "anabolic window." (8,9) This was based on the idea that the initial period of increased anabolic markers reflects an early period of bone formation relatively "unopposed" by resorption but then superseded by subsequent increases in bone resorption. This theory was not based on histomorphometric evidence of changing volumes of bone formation and resorption but rather inferred from finding an early increase in bone "formation" markers, followed by a later increase in bone "resorption" markers.Abaloparatide is a 34-amino acid peptide acting u...

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Expression of parathyroid hormone-related protein in cells of osteoblast lineage

Cited by 104 publications

References 47 publications

Expression of parathyroid hormone‐related peptide and insulin‐like growth factor I during rat fracture healing

Expression of parathyroid hormone‐related peptide and insulin‐like growth factor I during rat fracture healing

Histological assessments on the abnormalities of mouse epiphyseal chondrocytes with short term centrifugal loading

Abaloparatide Is an Anabolic, but Does It Spare Resorption?

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