FGF, a polypeptide found in brain and pituitary, provokes the initiation of DNA synthesis by resting ST3 cells. When glucocorticoids are present FGF stimulates DNA synthesis as effectively as serum.

Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth

Purification of the fibroblast growth factor activity from bovine brain.

Articular cartilage repair and regeneration continue to be largely intractable because of the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state of and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are also discussed.

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The Role of Tissue Engineering in Articular Cartilage Repair and Regeneration

Publisher Summary This chapter provides an overview of molecular characterization and the distribution and biological activities of fibroblast growth factor (FGF) in various tissues FGF in the pituitary plays a nonmitogenic role in the maintenance of prolactin and thyrotropin responsiveness, while the same molecule in macrophages may promote wound healing and in the corpus luteum angiogenesis It is based on the diverse biological activities of somatostatin in brain, hypothalamus, stomach, and pancreas and the wide distribution of numerous neuropeptides in both the central nervous system and the gastrointestinal tract The concept is equally applicable to FGF and perhaps other growth factors that show a wide distribution in many tissues The results presented in the chapter suggest that heretofore unidentified biologic activities may be related if not identical to acidic and basic FGFs These would include ovarian growth factor, macrophage-derived growth factor, cartilage growth factor, tumor angiogenic factor, eye-derived growth factor, retina-derived growth factor, corpus luteum angiogenic peptide, follicular angiogenic factor, adrenal vascularizing factor, and endothelial cell growth factors

Molecular characterization of fibroblast growth factor: distribution and biological activities in various tissues.

The control of proliferation of mesoderm-derived cells by EGF and FGF has been examined taking, as an example, the vascular endothelium. The mechanisms by which cell proliferation can be brought to a stop in vivo and in vitro have been reviewed.

Factors involved in the modulation of cell proliferation in vivo and in vitro: the role of fibroblast and epidermal growth factors in the proliferative response of mammalian cells.

A heat-labile anterior pituitary factor exerts a strong mitogenic action on articular chondrocytes in secondary monolayer culture. At the same time secretion of macromolecular radiosulfate into the medium by the stimulated cells is markedly reduced. This factor was found in NIH bovine and ovine TSH as well as LH but not in more purified (Condliffe-Bates, Pierce) preparations of TSH. The response, measured by the DNA content of the cell pellet, was dose-dependent; the lowest effective concentration was 1 μg NIH TSH/ml culture medium. The effect was fairly selective for chondrocytes, rabbit and human, and was displayed to much lesser degree by skin fibroblasts and 4 other cell types studied. FSH had a smaller effect while GH, prolactin, ACTH and a preparation having high EPS activity were relatively ineffective. Of 19 other hormone preparations examined, only crude HCG gave a comparable mitogenic response. Insulin, 0.1 U/ml, had a consistent but small effect. Estradiol-17β and diethylstilbesterol (10 μg/ml)...

A Pituitary Growth-Promoting Factor for Articular Chondrocytes in Monolayer Culture

Articular chondrocytes in primary monolayers or subcultures synthesize sulfated macromolecules, presumably mucopolysaccharides. Intracellular 35SO4 incorporation by postnatal rabbit chondrocytes reached a steady level by 24 hr of incubation; the nondialyzable extracellular (centrifuged medium + trypsin digest) counts increased over 72 hr, when they were up to 100 times the intracellular value. Cell for cell, radiosulfate counts in each fraction were higher in chondrocytes than fibroblasts. Data from a 3-year-old rabbit were comparable to those from recently weaned animals. Secretion of sulfated mucopolysaccharide was also found in cultures of adult human and bovine articular chondrocytes. Although Ham's F12 medium is advantageous in establishing a primary culture of chondrocytes, sulfate incorporation was greater when Dulbecco-Eagle medium, with or without supplemental L-proline, was used for subcultures. Ascorbic acid (5 mg/100 ml) added to an already confluent monolayer had no consistent effect.

Sulfate incorporation by articular chondrocytes in monolayer culture

A recently described pituitary chondrocyte growth factor (CGF) is a contaminant of several related glycoprotein hormones (TSH, LH and HCG). Chondrocytes were cultured from rabbits two to three months old. Bovine TSH (NIH) 69.5 μg/ml, used as the source of CGF, reduced the generation time from 16 to 10 hours through a virtual effacement of the G1 period. Incorporation of 3H-thymidine declined rapidly after 48 hours from maximal values (control 300 cpm/μg DNA; CGF, 679). Total DNA accumulated thereafter until 116 hours when the figures were 36 and 98 μg/flask, respectively. Little growth response occurred in spinner cultures. CGF lowered plating efficiency from 4.5 to 2.3%. The stimulatory effect diminished when CGF was removed from the medium. The treated cells were smaller and contained less protein and RNA than controls. They synthesized smaller quantitites of sulfated mucopolysaccharides (chondroitin sulfates 4,6 and doubly sulfated chondroitin as well as some dermatan sulfate) but hyaluronate production was not diminished.

Some biological characteristics of a pituitary growth factor (CGF) for cultured lapine articular chondrocytes.

Sir: Several tissue extracts are reported to increase the incorporation of sulfate by cartilage in vitro (1). Rumalon, a proprietary extract of bovine rib cartilage and bone marrow which has received numerous clinical trials in the treatment of osteoarthritis, is said to do the same (2). The preparation has been found to increase mucopolysaccharide production by mouse vertebral chondrocyte cultures (3) and to retard fibroblastic dedifferentiation of chick embryo chondrocytes in monolayers (4,5) . Our studies of articular chondrocytes and skin fibroblast monolayer cultures fail to support these findings and we think it worthwhile to place these observations on record. The experiments were carried out on secondary cultures of articular chondrocytes and skin fibroblasts from 2 rabbits about 10 weeks old using methods described previously (6.7) . A metacresolfree lot of Rumalon (no. 04101) was received through the generosity of Dr. W. P. Koella, Robapharm, Basel. According to data provided by the distributor, the inorganic sulfate content was 5.6 mg%: the vehicle, water: the osmolar freezing point depression At = -16°C. The culture medium was Dulbecco's, changed by substituting MgCl, for MgSO, so that it contained no inorganic sulfate. Adjustments were made to keep the several media isotonic and containing equal concentrations of inorganic sulfate. Thus, 0.15% NaaO, and 23.8% NaCl in Dulbecco's medium were added to 100 ml of the media in the quantities indicated in Table 1. The cells were inoculated into Falcon flasks with the media indicated in Table 1 as well as medium containing 2% Rumalon that had been immersed in a boiling water bath for 15 minutes. The cells were exposed to the test media for six days (fed day 0, 3, and 5 ) . On the day 5 feeding, Na, \"SO,, 1.4 &Ci/ml was added to the culture medium. The cells were harvested 20 hours later. The medium was dialyzed and counted by the methods we have already described. The DNA content of the cell pellet was measured by the method of Burton somewhat modified (7). The values obtained wert as indicated in Table 2. In trying to explain the disparity between thea and the published data, a question arises about the differentiation of these cells; were they capable of responding? The cultured chondrocytes probably have been altered from their native state but they do retain a unique capacity for making sulfated macromolecules (6) . Relative to rabbit articular chondrocytes considered as unit value, dpm %90,/pg DNA for other cell types are: human articular

Failure of rumalon to increase sulfate incorporation by articular chondrocytes in monolayer culture

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780150515

Charles J. Malemud

Papers

A Pituitary Growth-Promoting Factor for Articular Chondrocytes in Monolayer Culture

Sulfate incorporation by articular chondrocytes in monolayer culture

Some biological characteristics of a pituitary growth factor (CGF) for cultured lapine articular chondrocytes.

Failure of rumalon to increase sulfate incorporation by articular chondrocytes in monolayer culture

Rumalon and serum‐free culture of chondrocytes