Effects of Limited Exposure of Rabbit Chondrocyte Cultures to Parathyroid Hormone and Dibutyryl Adenosine 3′,5′-Monophosphate on Cartilage-Characteristic Proteoglycan Synthesis*

Kato, Yukio; Koike, Tatsuya; Iwamoto, Masahiro; Kinoshita, Masahiko; Sato, Katsuhiko; Hiraki, Yuji; Suzuki, Fujio

doi:10.1210/endo-122-5-1991

Cited by 29 publications

(9 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a relationship between cAMP and terminal differentiation and calcification of cultured chondrocytes has been clearly established (13), which could support the involvement of AM in the regulation of this process through its cAMP-dependent signal transduction system. Various other active factors that affect chondrocyte differentiation also increase the cAMP concentration in chondrocytes (17). The localization of AM, its mRNA, and the mRNA of its receptor to the growing skeletal structures and the fact that AM elicits its biological actions via the elevation of cAMP levels suggest an involvement of AM in embryonic chondrocyte maturation.…”

Section: Discussionmentioning

confidence: 99%

Expression of Adrenomedullin and Its Receptor during Embryogenesis Suggests Autocrine or Paracrine Modes of Action

et al. 1997

View full text Add to dashboard Cite

The present study reports the developmental patterns of expression of adrenomedullin (AM) in rat and mouse embryos. AM is a novel multifunctional peptide recently isolated from a human pheochromocytoma, which has been shown to promote growth in a variety of mammalian cell lines. We have applied several techniques to investigate the localization of both the AM peptide and its receptor throughout development. Immunocytochemical detection has been performed using different specific antibodies against AM and its generelated peptide pro-AM N-terminal 20 peptide. In situ hybridization showed the localization of the messenger RNAs for AM and its receptor. Western blot analysis together with reverse transcription-PCR gave further support to the localization of AM and its receptor in a variety of embryonic tissues. The localization of the receptor paralleled that of AM itself, suggesting an autocrine or paracrine mode of action. The spatio-temporal pattern of expression of AM in cardiovascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs is described. The primitive placenta, especially the giant trophoblastic cells, shows high levels of AM and AM receptor. The heart is the first organ that expresses AM during development. The kidney, lung, and developing tooth, in which epithelial-mesenchymal interactions are taking place, show specific patterns of AM expression. In several regions of the embryo, the patterns of AM expression correspond to the degree of differentiation. The possible involvement of AM in the control of embryonic invasion, proliferation, and differentiation is discussed. (Endocrinology 138: 440 -451, 1997) A DRENOMEDULLIN (AM) is a multifunctional peptide that has been identified from extracts of human pheochromocytoma (18). It is comprised of 52 amino acids and shows slight structural homology with calcitonin gene-related peptide (CGRP). Initial characterization demonstrated AM as a potent mediator of hypotension when injected iv into rats (18). AM and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), are the two known bioactive amidated peptides generated by posttranslational enzymatic processing of the 185-amino acid prepro-AM molecule (19). AM elevates intracellular cAMP levels in several cell types, and a receptor for AM (AM-R) has recently been cloned and sequenced (16). PAMP has no sequence homology with AM or CGRP and seems to act via a different receptor system (30). The expression of AM has been shown in a variety of adult rat, human, and porcine tissues, including heart, adrenals, brain, kidney, pancreas, aorta, lung, and brain-and lung-derived tumors (10,23,24,31).Apart from the vasorelaxant effect, several other functions have been reported for this peptide hormone. AM has been implicated in the regulation of renal function by means of its potent natriuretic and diuretic properties (14), has bronchodilatory effects (15), and inhibits the release of aldosterone, ACTH, and insulin (24,28). Recent data suggest the involv...

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of Adrenomedullin and Its Receptor during Embryogenesis Suggests Autocrine or Paracrine Modes of Action

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Although fewer studies have been conducted on the effects of PTH on cartilage cell growth and differentiation, it has been reported that this hor¬ mone is involved in cartilage development (25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Effects of parathyroid hormone fragments on the growth of murine mandibular condylar cartilage in vitro

Shurtz-Swirski

Lewinson²,

Shenzer³

et al. 1990

Acta Endocrinologica

View full text Add to dashboard Cite

The present study showed that the fragment hPTH (1-34) is mitogenic in organ cultures of neonatal mandibular condylar cartilage, and even more so in late fetal condyles. Three fragments of hPTH were used to clarify which part of the molecule possesses a mitogenic effect alike that of the native hormone: hPTH (1-34), and (53-84). [3H]thymidine incorporation into trichloracetic acid insoluble material and quantitative autoradiography were employed in a serum-free medium to assess the effects of these fragments while light and electron microscopy studies served for morphological evaluations. It became evident that the fragment hPTH (1-34) enhanced the incorporation of [3H]thymidine, a fact that could be noted only in serum-free medium. The putative target cells for the effects of hPTH (1-34) were the chondroporogenitor cells which also appeared to have experienced a blockage in their differentiation into chondroblasts. Ultrastructurally, the latter cells responded in the formation of adherent profiles of plasma membranes, whereas the differentiated zone of the cartilage reduced its size. Using serum-free medium, hPTH (1-34) also brought about an inhibition in alkaline phosphatase activity, a fact that was not encountered in medium containing serum. By contrast, hPTH (28-48) had no mitogenic effect, although treated specimens revealed morphological changes in the chondroprogenitor cell zone along with an enhancement of cartilage cells hypertrophy. No significant effects on either mitogenecity or morphology could be noted in hPTH (53-84)-treated cultures.Various in vivo studies with parathyroid hormone have shown that the epiphyseal growth plate usu¬ ally responds in a marked widening and in an in¬ crease in the number of chondroclasts along its ossification zone (1,2). These findings, along with others in earlier studies, appeared to suggest that PTH possesses a growth-stimulating effect on car¬ tilage. However, in order to gain further under¬ standing as to the mechanisms involved in the ac¬ tivity of PTH, one had to turn to in vitro studies. Kawashima et al. (3) carried out a series of organculture studies whereby the growth of cartilage of 9-day-old chick embryo femur was stimulated by PTH (500 U/l). In a subsequent study, Kawashima et al. (4) indicated that the stimulatory effects of PTH were exerted selectively upon the more mature, non-dividing hypertrophie chondrocytes, whereas younger cells did not respond to this hor¬ mone. Suzuki et al. (5) were the first to investigate the effects of PTH in tissue cultures of chon¬ drocytes isolated from growth cartilage of young male rats, finding that the hormone (100 (tg/1) in¬ duced a marked stimulatory effect upon the syn¬ thesis of proteoglycans. Takigawa et al. (6), who extended the original studies of Suzuki et al.,showed that PTH also increased the level of cAMP in chondrocytes, but had no effect upon DNA syn¬ thesis in cultured chondrocytes. Burch 8c Lebovitz (7) using chick pelvic cartilage in vitro, reported that PTH (10 nmol/1) increased the DNA content by 5...

show abstract

“…The increase in aggrecan synthesis was observed when the cells were treated for 20 or 4 h followed by a 16-h recovery in the absence of PTH. Previous studies using adult rabbit chondrocytes have demonstrated an effect of PTH only after a 24-h treatment and not within a 4-h treatment (25). These differences may be a reflection of species or developmental age or both.…”

Section: Fig 8 Reciprocal Relationship Between Aggrecan and Ig-fbp-mentioning

confidence: 91%

Parathyroid Hormone-(1–34) Enhances Aggrecan Synthesis via an Insulin-like Growth Factor-I Pathway

Frolik

Chandrasekhar

1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

During endochondral bone formation, the growth plate chondrocytes proliferate, become hypertrophic, lose the cartilage phenotype, undergo mineralization, and provide a scaffold upon which subsequent longitudinal bone growth occurs. Parathyroid hormone (PTH), a calcium-regulating hormone, and parathyroid hormone-related peptide (PTHrP), which shares several properties with PTH, have profound effects on skeletal growth and new bone formation. In order to define further the mechanism by which PTH/PTHrP promotes the cartilage phenotype, chondrocytes isolated from the rib cages of developing rat embryos were evaluated for the biosynthesis of aggrecan. Cells treated with PTH-(1-34) for a 4-h period followed by a 20-h recovery period showed a significant increase in cartilage proteoglycan (aggrecan) synthesis in a dose-dependent manner. Only N-terminally intact PTH and PTHrP were effective in stimulating aggrecan synthesis. Addition of a neutralizing antibody to insulin-like growth factor-I (IGF-I) during PTH treatment resulted in the inhibition of PTHstimulated aggrecan synthesis, whereas the addition of a neutralizing antibody to insulin-like growth factorbinding protein-2 (IGFBP-2) resulted in an increase in synthesis in both the control and PTH-treated cells. In addition, PTH treatment resulted in an increase in the mRNA for aggrecan, a reduction in IGFBP-3 mRNA, and no discernible changes in IGF-I mRNA levels, which was complemented by quantitative changes in IGFBP-3 and free IGF-I levels. The reciprocal relationship in the expression of aggrecan and IGFBP was further confirmed in chondrocytes from various gestational stages during normal development. Collectively, our results indicate that the effect of PTH may be mediated at least in part through the regulation of the IGF/IGFBP axis, by a decrease in the level of IGFBP-3, and an increase in free IGF-I levels. It is likely that the local increase in IGF-I may lead to an increase in cartilage type proteoglycan synthesis and maintenance of the cartilage phenotype.

show abstract

Effects of Limited Exposure of Rabbit Chondrocyte Cultures to Parathyroid Hormone and Dibutyryl Adenosine 3′,5′-Monophosphate on Cartilage-Characteristic Proteoglycan Synthesis*

Cited by 29 publications

References 27 publications

Expression of Adrenomedullin and Its Receptor during Embryogenesis Suggests Autocrine or Paracrine Modes of Action

Expression of Adrenomedullin and Its Receptor during Embryogenesis Suggests Autocrine or Paracrine Modes of Action

Effects of parathyroid hormone fragments on the growth of murine mandibular condylar cartilage in vitro

Parathyroid Hormone-(1–34) Enhances Aggrecan Synthesis via an Insulin-like Growth Factor-I Pathway

Contact Info

Product

Resources

About