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  • Author: Michael Silbermann x
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Michael Silbermann and Gila Maor

Abstract. The growth hormone of neonatal facial cartilage from ICR mice is inhibited by glucocorticoid treatment in vitro. A reduction of the overall tissue weight is accompanied by a substantial decrease in the protein content of the tissue. For the first 48 h in culture, hormone-treated cartilage undergoes a complete standstill in protein gain, and only thereafter the protein content increases, yet is markedly smaller than that of control specimens. Further, a significant reduction in the DNA content is seen already by 24 h, a feature that intensifies by 48 h. A slight recovery takes place thereafter. The reduction in DNA concentration is accompanied by a significant decrease in [3H]thymidine incorporation in acid-insoluble material. The inhibition of DNA synthesis by triamcinolone acetonide is protein- and RNA-synthesis-dependent. Autoradiographic examinations reveal that young cartilage cells are heavily labelled with [3H]dexamethasone and that this labelling is specific. To further substantiate the involvement of glucocorticoid-specific receptors in the latter's inhibitory effects, tissues were treated with cortexolone, this apparently 'masking' the cytosolic receptors for glucocorticoids, and thereby succeeded to eliminate the growth-inhibitory effect of triamcinolone. These results provide evidence for a receptor-mediated set of responses to glucocorticoids in these cartilage cells.

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Gila Maor, Zeev Hochberg and Michael Silbermann

Abstract. This study used an organ culture system of neonatal condylar cartilage to study the in vitro effects of recombinant human growth hormone on the growth of cartilage and its inherent cell populations: progenitor cells, chondroblasts and early hypertrophic chondrocytes. Growth hormone at a dose of 2.5 nmol/l enhanced the overall growth of cartilage explant and stimulated the differentiation of its cells. Hence, growth hormonetreated explants revealed a substantial increase in the number of chondroblasts and young hypertrophic chondrocytes. Along with its effects upon cartilage the hormone also stimulated new bone formation adjacent to mineralized hypertrophic chondrocytes. These results provide support to the notion that growth hormone stimulates cartilage growth which in turn is followed by endochondral ossification. In spite of its in vitro effect it is not as yet clear whether the effect of growth hormone is indeed a direct one or is mediated via the local production of IGF-I.

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Gila Maor, Zeev Hochberg and Michael Silbermann

The present study examined the effect of exogenous IGF-I on growth and development of neonatal cartilage of the mandible condyle. Condylar cartilage was cultured as organ culture. The explants were cultured on top of collagen sponges in medium containing 2% fetal calf serum and were treated with IGF-I at doses ranging from 3.25 to 26 nmol/l for up to six days. IGF-I was found to increase significantly the uptake of [3H]-thymidine and [35S]-sulfatein a dose-related manner. The enhanced cellular proliferation, along with the increased synthesis of proteoglycans, resulted in a substantially larger mass of tissue in the organ culture system. The nature of the IGF-I stimulative effect was further studied through the use of a tissue culture system whereby a separated chondroprogenitor zone is cultured under conditions which favor its development at first into cartilage and then into bone. Using this culture system, we could show that IGF-I induces merely the de novo chondrogenesis process. This was reflected in the appearance of relatively large amounts of cartilage specific antigens such as type II collagen, cartilage proteoglycans, chondrocalcin and 100 KDa protein. Yet, no bone specific antigens were significantly increased, as is the case with GH effects. These results indicate that IGF-I is a strong chondrogenetic agent. But, unlike growth hormone, it does not seem to stimulate bone formation.

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Revital Shurtz-Swirski, Dina Lewinson, Pesia Shenzer, Hubert Mayer and Michael Silbermann

Abstract

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), (28–48) 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.