Cartilage-stimulating activity

It is almost three decades since Salmon and Daughaday (S3) described a GH-dependent serum factor which could stimulate sulfate incorporation by cartilage in vitro, an activity apparently not inherent in GH itself. This sulfation factor was postulated to mediate the known effects of GH in vivo on skeletal growth. Subsequent studies revealed a range of GH-dependent activities in rat cartilage stimulation of sulfate and leucine uptake into glucosaminoglycans (S4), proline conversion to collagen hydroxyproline (D3), and incorporation of uridine into RNA and thymidine into DNA (Gl,... 

GH primarily displays an anabolic activity. It partially stimulates the growth of bone, muscle and cartilage cells directly. Binding of GH to its hepatic receptor results in the synthesis and release of... 

In response to an unknown stimulus, lymphocytes migrate into the synovium and secrete cytokines. These then activate lymphocyte proliferation, stimulate antibody production by B lymphocytes and activate macrophages. The activated macrophages themselves secrete their own repertoire of cytokines and can also secrete proteases, which then contribute to cartilage de-... 

GH primarily displays an anabolic activity. It partially stimulates the growth of bone, muscle and cartilage cells directly. Binding of GH to its hepatic receptor results in the synthesis and release of insulin-like growth factor (IGF-1), which mediates most of GH s growth-promoting activity on, for example, bone and skeletal muscle (Chapter 7). The major effeets mediated by hGH are summarized in Table 8.6. 

TNF-a and IL-1 are current targets of antiinflammatory drug therapy. A homotrimer of 17-kDa protein subunits whose effects include the activation of neutrophils and eosinophils, induction of COX-2, induction of proinflammatory cytokines (e.g., IL-1, IL-6), enhancement of endothelial layer permeabihty, induction of adhesion molecules by endothelial cells and leukocytes, stimulation of fibroblast proliferation, degradation of cartilage, and stimulation of bone reabsorption. Two receptors mediate these effects a 55-kDa receptor (p55) and a 75-kDa receptor (p75). Each of these receptors is found in both cell surface and soluble forms. The binding of two or three cell surface receptors to TNF-a initiates an inflammatory response. Soluble p55 also acts as a signaling receptor for inflammatory responses, whereas soluble p75 acts as an antagonist. 

Cell metabolism induction. Methanol extract of STE, in collagen-producing cells, stimulated glycolysis by 80% in cartilage but was not affected in the other tissues. Medium alkaline phosphatase activity was unaffected. In the frontal bone and cartilage, [ H]hydroxyproline and [ H]proline contents were decreased. Neither was affected in the aorta. 

The relationship of serum calcium and phosphate with rickets was discovered by Howland and Kramer [10]. They found that blood from normal rats could mineralize rachitic rat cartilage, whereas blood from rachitic rats could not. They also provided evidence that a low serum calcium and phosphate status caused rickets. Orr etal. [11] demonstrated that UV irradiation stimulated calcium absorption. This study was largely unappreciated for 30 years until Nicolaysen and Eeg-Larsen [12] and Schachter and Rosen [13] demonstrated evidence for vitamin D-induced intestinal absorption of calcium by an active transport process. 

Bone resorption occurs when osteoclasts are activated to produce proteases and collagenase by parathyroid hormone or by osteoclast activating factor (derived from phytohemagglutinin stimulated lymphocytes). Although trasylol and soybean trypsin Inhibitor do not affect bone resorption, a specific cartilage-derived antl-collagenase seems to be active. 

Salmon, W. D., Jr., and DuVall, M. R., A serum fiaction with suliation factor activity stimulates in vitro incorporation of leucine and sulfiite into protein-polysaccharide complexes, uridine into ENA and thymidine into DNA of costal cartilage from hypophysectomized rats. Endocrinology (Baltimore) 86, 721-727 (1970). 

---