Hormonal Regulation of Bone Formation

Raisz, Lawrence G.; Canalis, Ernesto; Dietrich, John W.; Kream, Barbara E.; Gworek, Susan C.

doi:10.1016/b978-0-12-571134-0.50013-2

Cited by 35 publications

(22 citation statements)

References 41 publications

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“…In 21-day fetal rat calvaria maintained in organ culture for hr, PTH at I nM to gM decreases the incorporation of [3H]proline into collagenase-digestible protein (CDP) but has little effect on the labeling of noncollagen protein (NCP) (4). During this interval, characteristic polygonal osteoblasts are replaced by spindle-shaped cells (5), and net accumulation of bone collagen decreases (6). Similarly, PTH inhibits the synthesis of collagen in osteoblast-like cells derived from 2-to 3-day mouse calvaria by sequential enzymatic digestion (7).…”

mentioning

confidence: 99%

Parathyroid hormone alters collagen synthesis and procollagen mRNA levels in fetal rat calvaria.

Kream¹,

Rowe²,

Gworek³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

118

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Parathyroid hormone decreased the incorpo- (5), and net accumulation of bone collagen decreases (6). Similarly, PTH inhibits the synthesis of collagen in osteoblast-like cells derived from 2-to 3-day mouse calvaria by sequential enzymatic digestion (7). The molecular mechanism by which PTH alters collagen synthesis in these bone cultures is unknown. Because procollagen mRNA levels appears to be the primary regulatory site for changes in collagen synthesis in embryonic chicken calvaria (8), a likely hypothesis is that PTH regulates collagen synthesis in fetal rat bone by altering the level of procollagen mRNA. On the other hand, PTH is a potent stimulator of bone resorption (9, 10) and could have a posttranslational effect on collagen levels by enhancing the degradation of newly synthesized collagen.One objective of the present study was to determine whether the ability of PTH to inhibit collagen synthesis in cultures of fetal rat calvaria could be correlated with alterations in the level of functional procollagen mRNA. Another was to assess the effect of PTH on the release of newly synthesized collagen from these calvaria into the culture medium. Our results demonstrate that PTH decreases both collagen synthesis and the bone level of procollagen mRNA but has only a small effect on the release of collagen into the medium, indicating that PTH regulates collagen synthesis primarily through an effect on procollagen mRNA levels.MATERIALS AND METHODS Culture Method. The frontal and parietal bones were removed from 21-day fetal rats (Sprague-Dawley; Charles River Breeding Laboratories) and split along the sagittal suture. Half calvaria were cultured at 370C under a humidified atmosphere of 5% C02/95% air in 25-ml erlenmeyer flasks containing 2 ml of modified BGJ medium (11) supplemented with bovine serum albumin at 1 mg/ml or with 5% human serum that had been heated at 56°C for 30 min. The concentration of unlabeled proline in the medium was 1 mM except where indicated. Half calvaria were cultured for 24 hr with continuous shaking (60 oscillations per min) at 370C. Either natural bovine PTH 1-84 (National Institutes of Health) or the synthetic bovine 1-34 peptide (Beckman) was added to cultures in a solution containing 1 mg of bovine serum albumin per ml. During the final portion of the culture period, 5-10,uCi of [2,3-3H]proline (30 Ci/mmol; 1 Ci = 3.7 X 1010 becquerels; New England Nuclear) was added to each flask for 15-120 min. To terminate the culture each calvarium was removed, extracted with 5% trichloroacetic acid, acetone, and ether and then dried, weighed, and homogenized in 1.0 ml of 0.5 M acetic acid.The incorporation of [3H]proline into CDP and NCP was determined by using repurified bacterial collagenase (Worthington) according to the method of Peterkofsky and Diegelmann (12) and was linear for at least 120 min in both control and PTH-treated calvaria (Fig. 1). The percentage collagen synthesized by the bones was corrected for the relative abundance of proline residues in collagen compared to NCP ...

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mentioning

confidence: 99%

Parathyroid hormone alters collagen synthesis and procollagen mRNA levels in fetal rat calvaria.

Kream¹,

Rowe²,

Gworek³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

118

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“…Insulin and IGF-I have similar effects on collagen synthesis [5,14]. IGF-I stimulates the synthesis of DNA at physiological concentrations, but insulin increased DNA synthesis only at high concentrations in cultured bone [3].…”

Section: Discussionmentioning

confidence: 90%

“…The effects of insulin on calcification were recognized in a mouse longbone culture system [4]. However, these effects were not significant in cultured fetal rat parietal bones [5]. Recently, Gronowicz et al [6] developed a mineralizing serum-free organ culture system of fetal rat parietal bones, in which system, insulin at a concentration of 10_6 M was added as one component of the medium.…”

Section: Effects Of Insulinmentioning

confidence: 99%

Effects of Insulin on In Vitro Bone Formation in Fetal Rat Parietal Bone.

1994

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Abstract.We examined the effects of insulin on bone formation including the mineralizing process. Twenty-day fetal rat parietal bones were cultured for 96 h on grids in a serum-free medium. For the precise assessment of bone formation, histomorphometry, with an image analyzing system, was used to measure the areas of mineralized bone and bone matrix, and the numbers of osteoblasts and osteoclasts. In order to confirm the effects of insulin on bone mineralization, the calcium content of the bone and the release of previously incorporated 45Ca into the medium were measured. Insulin, at a concentration of 10-6 M or higher, increased the areas of mineralized bone and bone matrix, and the number of osteoblasts. Osteoclasts were seldom observed in bones on day 0 or in bones treated with insulin. In bones treated with insulin at a concentration of 10-6 M, the calcium content of bone increased. At an insulin concentration of 10-' M or higher, the dry weight of decalcified bone increased. Lactate production in the medium increased dose-dependently. The inhibited release of 45Ca in bones indicated that insulin acts by increasing calcium retention. We demonstrated that insulin has an effect on bone-forming and bone-resorbing cells to enhance the bone forming process from matrix formation to mineralization.

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“…These results may have important clinical implications in the use of steroids as antiinflammatory drugs. The slight but statistically significant increase of noncollagenous proteins in cell population II may have been due to a permissive action of glucocorticoids on growthsupporting hormones or factors that regulate bone metabolism [39].…”

Section: Discussionmentioning

confidence: 99%

Comparative study of deflazacort, a new synthetic corticosteroid, and dexamethasone on the synthesis of collagen in different rat bone cell populations and rabbit articular chondrocytes

1984

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Deflazacort is a new synthetic glucocorticoid which is an oxazoline derivative of prednisolone. In previous studies, it was shown that deflazacort, depending on the test model used, not only showed considerably more antiinflammatory potency than prednisolone in animals but also caused less deleterious effects on bone mineral metabolism than equivalent amounts of other glucocorticoids in man. In this study, we have compared the effects of deflazacort with those of dexamethasone on the synthesis of collagen in various rat bone cell populations and chondrocytes. Three bone cell populations were prepared by sequential time-dependent collagenase treatment of 1-day-old rat calvaria. Each cell population was further purified on a Percoll gradient (10-90%) yielding three populations of which two are different in alkaline and acid phosphatase and response to parathyroid hormone. A 3-day treatment of bone cell populations with deflazacort and dexamethasone (10(-11)-10(-5) M) revealed that both glucocorticoids, although at different concentrations, inhibited collagen synthesis. 21-desacetyl-deflazacort (5 beta, 11 beta, 16 beta)-11,21-dihydroxy-2'-methyl-5-H-pregna-1-enol [17,16-d]oxazole-3,20-dione), the presumably active form of the steroid, which is formed in vivo after administration, produced nearly identical results as its precursor. Glucocorticoid concentrations at which inhibition was initially observed were 10(-9) M and 10(-7) M for dexamethasone and deflazacort respectively. Inhibition of collagen synthesis was significantly impaired only in cells isolated from bone during early tissue digestion, and not in those obtained during extensive collagenase treatment. Chondrocytes isolated from articular cartilage of 3-month-old rabbits and grown in primary cultures did not respond to either steroid.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hormonal Regulation of Bone Formation

Cited by 35 publications

References 41 publications

Parathyroid hormone alters collagen synthesis and procollagen mRNA levels in fetal rat calvaria.

Parathyroid hormone alters collagen synthesis and procollagen mRNA levels in fetal rat calvaria.

Effects of Insulin on In Vitro Bone Formation in Fetal Rat Parietal Bone.

Comparative study of deflazacort, a new synthetic corticosteroid, and dexamethasone on the synthesis of collagen in different rat bone cell populations and rabbit articular chondrocytes

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