Chondrocytes synthesis

Vitamin D may regulate calcification of cartilage by regulating chondrocyte synthesis of proteoglycans. l,25(OH)2D3, an active metabolite of vitamin D has been shown to produce a concentration-dependent reduction in an immortalized rat chondrocyte cell line. Both vitamin D and l,25(OH)2D3 are considered secosteroids with vitamin D receptors, which includes cytosolic/nuclear proteins that bind specifically to the secosteroid as it transits the plasma membrane. 

Chitosan freeze-dried fleeces support chondrocyte attachment and synthesis of extracellular matrix [344]. Chitosan was used to assist the spontaneous tissue repair of the meniscus [345]. The repair of the cartilage and the prevention of its degradation in osteoarthritis is, however, possible with the association of glucosamine sulfate salt and chondroitine sulfate, the latter being particularly effective [346]. 

Setton and Chilkoti applied ELPs as a three-dimensional matrix to entrap chondrocytes. In their study, ELP[VsG3A2-90] with a transition temperature of 35°C at 50 mg/mL in PBS was used. This biopolymer can be used to generate a suspension with cells, which upon injection into a defect site will form a scaffold. They showed that in vitro the resulting ELP gel supported the viability of chondrocytes and the synthesis and accumulation of cartilage-specific extracellular matrix material. This suggested that ELPs indeed could be used for in situ formation... 

Reactive nitrogen species are another factor of free radical damage in rheumatoid arthritis, although their role is less studied than that of oxygen radicals. Stichtenoth and Frolich [242] pointed out that the inhibition of nitric oxide synthesis had beneficial effects in humans. Mazzetti et al. [243] found that IL-1(3 stimulated NO production in RA chondrocytes. We demonstrated that NO synthase of RA neutrophils generated the enhanced amount of peroxynitrite [234]. Nitric oxide and oxygen radicals are also important inducers of death of human osteoarthritic synoviocytes [244]. 

Lubberts E, Joosten LA, van de Loo FA, van den Gersselaar LA, van den Berg WB Reduction of interleukin-17-induced inhibihon of chondrocyte proteoglycan synthesis in intact murine articular carhlage by interleukin-4. Arthritis Rheum 2000 43 1300-1306. 

Collier S, Ghosh R Comparison of the effects of NSAIDs on proteoglycan synthesis by articular cartilage explant and chondrocyte monolayer cultures. Biochem Pharmacol. 1991 41 1375-1384. 

ECMs contain a variety of cell types (see Table 1.2) such as fibroblasts in the skin, chondrocytes in cartilage, and osteoblasts in bone. The role of these cells is to synthesize and deposit the ECM surrounding the cell and to change the amount and location of the ECM in response to trauma and changes in external loading. For instance, collagen synthesis in these cells is typically up-regulated by the application tensile forces and is down-... 

Smith RL, Rusk SF, Ellison BE, Wessells P, Tsuchiya K, Carter DR, Caler WE, Sandell LJ, Schurman DJ. In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure. J Orthop Res. 1996 14 53-60. 

In primary cultures, articular chondrocytes grown in an artificial matrix after digestion of the original one, maintain their characteristic synthesis and turnover rate of cartilage matrix macromolecules... 

The described method is suitable to compare up to 50 drugs in one experiment. The price for this is the limited quantification, as the staining is not strictly stoichiometric, and does not allow the distinction between matrix synthesis and degradation. For more detailed assessment, radiolabeling is the better choice. The limitation of these primary culture assays lies in the elaborate preparation and isolation of the chondrocytes. Several attempts to immortalize this differentiated mesenchymal cell type have so far resulted in the loss of certain cartilage-specific properties. 

Malemud CJ, Stevenson S, Mehraban F et al. (1994) The proteoglycan synthesis repertoire of rabbit chondrocytes maintained in type II collagen gels. Osteoarthritis and Cartilage 2 29-42... 

Verbruggen G, Veys EM, Wieme N et al. (1990) The synthesis and immobilisation of cartilage-specific proteoglycan by human chondrocytes in different concentrations of agarose. Clin Exp Rheumatol 8 371-378... 

Calcitriol modulates the maturation of chondrocytes via a cell surface receptor linked to phospholipase and protein kinase C in response to calcitriol, there are rapid changes in arachidonic acid release from, and reincorporation into, membrane phospholipids, and increased synthesis of prostaglandins Ei and E2 (Boyan et al., 1999). 24-Hydroxycalcidiol also modulates the maturation of chondrocytes, acting via cell surface receptors linked to phospholipase D, causing inactivation of both protein kinase C and MAP kinases, thus... 

Two further perspectives on the use of tetracychnes in rheumatoid arthritis have been pubhshed (14,15). In addition to an effect on matrix metalloproteinases, the authors focused on a potential antiarthritic action of tetracyclines by their effects in the interaction between the generation of nitric oxide, matrix metalloproteinase release, and chondrocyte apoptosis. Both minocychne and doxycycline inhibit the production of nitric oxide from human cartilage and murine macrophages (16) in concentrations that are achieved in vivo. The authors suggested that tetracyclines may have several potential chondroprotective effects direct inhibition of matrix metalloproteinase activity and, by inhibition of nitric oxide production, further reduction of matrix metalloproteinase activity, reversal of reduced matrix synthesis, and reduced chondrocyte apoptosis. 

Pelletier J, Mineau F, Raynauld J et al 1994 Intraarticular injections with methylprednisolone acetate reduce osteoarthritic lesions in parallel with chondrocyte stromelysin synthesis in experimental osteoarthritis. Arthritis and Rheumatism 37 414-423... 

In other studies, NSAIDs, such as carprofen and benoxaprofen, have been reported to increase proteoglycan synthesis in cartilage explants and chondrocytes (Mcllwraith 1996, Palmoski Brandt 1983). Obviously, more work is needed to determine the effects of NSAIDs on normal and arthritic joints. 

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