Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin.

Abstract

We have used a catheterization system that permits chronic infusion into the arterial supply of one hindlimb of rats to study the direct effects of rat growth hormone and human somatomedin C on growth of the tibial epiphyseal cartilage plate in hypophysectomized rats. Rat growth hormone (0.4 ,.g per day) or human somatomedin C (0.25, 1, or 4 ,ug per day) stimulated growth of the epiphyseal plate of the infused limb but not of that of the contralateral noninfused limb. The somatomedin C had a dose-related effect. Rabbit antiserum to human somatomedin C, but not normal rabbit serum, completely abolished the direct growth effect of the rat growth hormone when it was co-infused with the hormone. These results support the concept that growth hormone stimulates long bone growth by inducing local production of somatomedin, which in turn stimulates cell proliferation in an autocrine or paracrine fashion. However, they do not exclude the possibility that serum somatomedin may also play a role.The somatomedin hypothesis of Salmon and Daughaday (1) maintains that the growth-promoting actions of growth hormone (GH) are indirect and act via GH-dependent plasma factors named somatomedins or insulin-like growth factors. This hypothesis has evolved to include the concept that somatomedins are produced primarily by the liver in response to GH (2-4). Although most of the early evidence in support of this theory was derived from in vitro work, Schoenle et al. (5) recently demonstrated a dose-related growth-promoting effect of systemically infused human somatomedin (hSm) on the proximal tibial epiphyseal plate of hypophysectomized rats. However, a local effect of GH on tibial cartilage growth has also been demonstrated in hypophysectomized rats in vivo by direct injection into the proximal tibial epiphyseal plate (6, 7), by intraarticular injection into the knee joint or administration into the epiphysis by implanted cannula (8), and by chronic infusion into the arterial supply of one hindlimb (9). In addition, numerous cells and tissues have been shown to produce somatomedins in vitro, either spontaneously or in response to GH (10-18). Thus, it is possible that GH exerts its direct effects by stimulating local production of somatomedins.To investigate this possibility we used the system of Schlechter et al. (9), which permits chronic infusion into the arterial supply of one hindlimb of a rat. With this procedure, we have demonstrated a direct growth-promoting effect of human somatomedin C (hSm-C) on the proximal tibial epiphyseal plate of hypophysectomized rats. In addition, we have found that the local effect of rat GH (rGH) could be completely abolished by co-infusing an antiserum raised against hSm-C. MATERIALS AND METHODSMale Long-Evans rats (125-150 g) were obtained from our breeding colony. Husbandry conditions were as described (9). The animals were hypophysectomized by the transauricular approach (19) 14 days prior to catheterization. On the day of catheterization, they were reanesthetized (9) and the right superi...

WISP3‐dependent regulation of type II collagen and aggrecan production in chondrocytes

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Differential Morphology and Homogeneity of Tissue-Engineered Cartilage in Hydrodynamic Cultivation with Transient Exposure to Insulin-Like Growth Factor-1 and Transforming Growth Factor-β1

“…3B, left) cultures, indicating that the need for each growth factor in chondrocytes is governed by differential mechanisms. The final growth factor concentrations in waste media measured in all of the groups were higher than those added to fresh media, suggesting that chondrocytes possess the ability to secrete endogenous IGF-1 28,29 and TGF-b 30,31 for selfsupplementation such that their desire for exogenous growth factors gradually decreases. It has also been demonstrated that both IGF-1 and TGF-b are shear-responsive factors, meaning their expression and synthesis can be promoted by fluid shear stress.…”

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