Collagen Synthesis In Cartilage Research Articles

Serum N-propeptide of collagen IIA (PIIANP) as a marker of radiographic osteoarthritis burden.

ObjectiveCartilage homeostasis relies on a balance of catabolism and anabolism of cartilage matrix. Our goal was to evaluate the burden of radiographic osteoarthritis and serum levels of type IIA procollagen amino terminal propeptide (sPIIANP), a biomarker representing type II collagen synthesis, in osteoarthritis.MethodsOA burden was quantified on the basis of radiographic features as total joint faces with an osteophyte, joint space narrowing, or in the spine, disc space narrowing. sPIIANP was measured in 1,235 participants from the Genetics of Generalized Osteoarthritis study using a competitive enzyme-linked immunosorbent assay. Separate multivariable linear regression models, adjusted for age, sex, and body mass index and additionally for ipsilateral osteophytes or joint/disc space narrowing, were used to assess the independent association of sPIIANP with osteophytes and with joint/disc space narrowing burden in knees, hips, hands and spine, individually and together.ResultsAfter full adjustment, sPIIANP was significantly associated with a lesser burden of hip joint space narrowing and knee osteophytes. sPIIANP was associated with a lesser burden of hand joint space narrowing but a greater burden of hand osteophytes; these results were only evident upon adjustment for osteoarthritic features in all other joints. There were no associations of sPIIANP and features of spine osteoarthritis.ConclusionsHigher cartilage collagen synthesis, as reflected in systemic PIIANP concentrations, was associated with lesser burden of osteoarthritic features in lower extremity joints (knees and hips), even accounting for osteoarthritis burden in hands and spine, age, sex and body mass index. These results suggest that pro-anabolic agents may be appropriate for early treatment to prevent severe lower extremity large joint osteoarthritis.

The Chick α2(I) Collagen Gene Contains Two Functional Promoters, and Its Expression in Chondrocytes Is Regulated at Both Transcriptional and Post-transcriptional Levels

Embryonic chick cartilages contain transcripts derived from the alpha2(I) collagen gene, although type I collagen is not normally found in these tissues; most of these RNAs are alternative transcripts initiating within intron 2. Use of the internal start site results in replacement of exons 1 and 2 with a previously undescribed exon and a change in the translational reading frame; thus, the alternative transcript cannot encode alpha2(I) collagen. We have demonstrated that production of the alternative transcript is due to activation of an internal promoter in chondrocytes and have identified a 179-base pair domain that is required for its activity. Furthermore, we have shown that the alternative transcript resulting from activation of the internal promoter turns over relatively rapidly; thus, the steady-state level of this transcript is less than predicted based on the transcription rate. The upstream promoter is only partially repressed in chondrocytes, suggesting that the lack of authentic alpha2(I) collagen mRNA may also be due in part to decreased mRNA stability. Thus, repression of alpha2(I) collagen synthesis in cartilage involves both transcriptional and post-transcriptional mechanisms. In contrast, repression of alpha1(I) collagen synthesis appears to be mediated primarily at the level of transcription.

Effects of certain antiarthritic agents on the synthesis of type II collagen and glycosaminoglycans in rat chondrosarcoma cultures.

Cartilage destruction is a characteristic feature of osteoarthritis. Treatment with certain nonsteroidal anti-inflammatory drugs could exacerbate cartilage destruction by impairing the synthesis of cartilage matrix proteins, type II collagen and proteoglycan. In order to monitor the changes occurring in cartilage collagen synthesis, we developed a type II collagen specific ELISA. The effects of antiarthritic agents on type II collagen and glycosaminoglycan synthesis were examined in rat chondrosarcoma cultures. Drugs were added to the monolayer cultures and 4 days later the total type II collagen, as determined by the type II collagen ELISA, and glycosaminoglycan content, as measured by dimethyl-methylene blue dye binding assay, was measured. All drugs except tiaprofenic acid decreased type II collagen synthesis by at least 40% at 100 micrograms/ml. Tiaprofenic acid at 1 microgram/ml increased type II collagen content by 54% of the controls. Glycosaminoglycan synthesis was decreased by acetylsalicylic acid, diclofenac and tiaprofenac acid, at 50 micrograms/ml or above. Indomethacin, naproxen and dexamethasone had no effect. Interestingly, tenidap stimulated the glycosaminoglycan synthesis by 32% at 100 micrograms/ml. We show that the combination of chondrosarcoma cultures, type II collagen specific ELISA and dimethylmethylene blue dye binding assay serves as a useful model for screening the effects of agents capable of modulating type II collagen and glycosaminoglycan synthesis.

Oxygen radical formation by epiphyseal chondrocytes causes changes in cartilage collagen synthesis

Oxygen radical formation by epiphyseal chondrocytes causes changes in cartilage collagen synthesis

Effects of joint loading on articular cartilage collagen metabolism: assay of procollagen prolyl 4-hydroxylase and galactosylhydroxylysyl glucosyltransferase.

The degree of joint loading on the femoral head cartilage was experimentally altered in dogs by splinting of the knee joint for 11 weeks (n = 9), and making another group (n = 6) to run on a treadmill with 15 degrees uphill inclination during a period of 15 weeks (4 km/day, 5 days a week). A third group (n = 9) served as controls. The influence of these altered loading conditions on articular cartilage collagen synthesis was measured by assaying the activity of procollagen prolyl 4-hydroxylase (PPH) and galactosylhydroxylysyl glucosyltransferase (GGT) in chondrocytes. The average activity of PPH was 11-13% elevated in the runner and contralateral (more loaded) cartilages, while the splinted (unloaded) cartilages showed a significant (53%) increase of PPH. In some samples of the runner, splinted and contralateral cartilages the activity of GGT was also high, but the differences did not reach statistical significance. The increase of the activity of PPH, combined with unaltered total content of collagen, indicates that the synthesis of collagen and probably also its turnover, are enhanced in the cartilage atrophied due to reduced weight-bearing, but only slightly, if at all in the cartilages subjected to moderately elevated loading.

The effect of inorganic orthophosphate on the rates of collagen formation and degradation in bone and cartilage in tissue culture.

ABSTRACT Using a tissue culture system, the effect of the concentration of inorganic orthophosphate [(Pi)] in the tissue culture medium on the synthesis and degradation of collagen in bone and cartilage was studied. A consistent observation was that the rate of synthesis of bone and cartilage collagen was markedly reduced when the [(Pi)] concentration of the tissue culture medium was lowered to 0.32 mm. In addition, less of the collagen that was synthesized was incorporated into the tissue. Increasing the [(Pi)] concentration beyond 1.30 mm (a concentration at which this effect was reversed) to concentrations as high as 3.23 mm of [(Pi)] did not significantly alter the rate of collagen synthesis in cartilage or bone. The [(Pi)] concentration in the tissue culture medium affected the rate at which the older structural collagen was degraded only when the rate of bone collagen resorption was elevated by increasing the O2 tension in the culture chamber and especially when, in addition to increasing the O2 ten...

Biochemical Studies on Developing Canine Hip Joints

Biochemical studies done on the connective tissues of hip joints from beagles at different ages showed that the DNA and hexosamine content were reduced by about 50 per cent from birth to one year of age in articular cartilage, while the hydroxyproline content increased with age. The connective tissues of hip joints contained measurable quantities of soluble collagen at birth, but as animals became older, soluble collagen content diminished, and after six months of age essentially only insoluble collagen was found. The rates of protein and polysaccharide formation were significantly higher in the samples from newborn puppies than in those from one-year-old dogs; the rate of collagen synthesis in cartilage decreased dramatically. The data indicated that metabolic activity per individual cell was reduced in the cartilage samples from mature dogs. The hydrolytic enzyme activities decreased in the tissues with age, primarily because of a decreased number of cells per unit weight of cartilage.

Sites of earliest collagen-formation in the chick embryo, as indicated by uptake of tritiated proline

The uptake of tritiated l-proline into tissues of chick embryos from 1–9 days' incubation age has been investigated autoradiographically. In a first series, 48-hr embryos were grown on egg/agar medium containing 50 μC/ml tritiated proline; in a second series, 10 μC tritiated proline was injected immediately underneath the blastoderm of unincubated eggs; in the third series embryos of three days and older received injections of 10 μC tritiated proline into the heart. Embryos of the first series showed immediate uptake of proline into all tissues equally, as judged by autoradiographs. Embryos of both the second and third series showed highest uptake of radioactivity in the chorda, from 3 days onwards, and later also a high uptake in sclerotome and dermatome. These findings may represent events that precede or accompany collagen synthesis in cartilage and skin. Histological findings support this suggestion.