Chondrocytes, synoviocytes and dermal fibroblasts all express PH-20, a hyaluronidase active at neutral pH

Hyaluronan (HA), an important component of connective tissues, is highly metabolically active, but the mechanisms involved in its catabolism are still largely unknown. We hypothesized that a protein similar to sperm PH-20, the only mammalian hyaluronidase known to be active at neutral pH, could be expressed in connective tissue cells. An mRNA transcript similar to that of PH-20 was found in chondrocytes, synoviocytes, and dermal fibroblasts, and its levels were enhanced upon stimulation with IL-1. In cell layers extracted with Triton X-100 – but not with octylglucoside – and in culture media, a polyclonal antipeptide anti-PH-20 antibody identified protein bands with a molecular weight similar to that of sperm PH-20 (60 to 65 kDa) and exhibiting a hyaluronidase activity at neutral pH. Further, upon stimulation with IL-1, the amounts of the neutral-active hyaluronidase increased in both cell layers and culture media. These findings contribute potential important new insights into the biology of connective tissues. It is likely that PH-20 facilitates cell-receptor-mediated uptake of HA, while overexpression or uncontrolled expression of the enzyme can cause great havoc to connective tissues: not only does HA fragmentation compromise the structural integrity of tissues, but also the HA fragments generated are highly angiogenic and are potent inducers of proinflammatory cytokines. On the other hand, the enzyme activity may account for the progressive depletion of HA seen in osteoarthritis cartilage, a depletion that is believed to play an important role in the apparent irreversibility of this disease process

Bêta-2-microglobuline et affections rhumatismales.

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L'exploration scintigraphique dans l'algodystrophie sympathique réflexe

Three-phase radionuclide bone scanning is extremely useful in patients with suspected reflex sympathetic dystrophy syndrome. The functional data it provides can be analyzed either visually or semiquantitatively. Its many advantages include good sensitivity; however, its specificity varies substantially across sites and clinical patterns. The main differential diagnoses are reviewed. Semiquantitative analysis of scintigram data is of limited diagnostic usefulness but provides valuable pathophysiological information and can be helpful in guiding therapeutic decisions. Semiquantitative analysis has demonstrated that the severity and duration of changes in radionuclide uptake vary widely across sites and that effects on scintigraphic parameters differ between calcitonin and pamidronate

Proteoglycan aggregates in normal and osteoarthritic cartilage

Early investigators believed that articular cartilage was an inert material lacking internal structure. During the last decades, studies have however provided strong evidence that articular cartilage was a metabolically active tissue comprising an elaborated framework of macromolecules. It is also clear that this fascinating tissue is heterogeneous at the structural biochemical and cellular levels. The finding that native PG aggregates can be divided into two well-characterized families- ie the less saturated or slow sedimenting and the more saturated or fast sedimenting aggregates – point out that the phenomenon of PG aggregation is more variable and complex than initially conceived. Further the exact sites in the HA binding domains of both PG and link protein molecules have not yet been defined and the details of the spatial arrangement of HA, link protein and the G1 domain of PGs in the central backbone of aggregated are not yet known. The clear-cut difference in the size distribution of the two populations of aggregates is related to their dissimilar content on HA and link protein but not to the size of HA molecules. We do not have a final explanation on how the same HA molecules induce the formation of two well-defined families of PG aggregates; however, we provide strong evidence that link protein not only stabilizes PG aggregates against dissociation but also induces the formation of more saturated and larger PG aggregates. These findings emphasize the necessity to better understand the exact mechanisms governing the synthesis and extracellular assembly of aggregates constituents. This requirement is further compounded by the observation that newly synthesized Pgs are no longer incorporated into larger aggregates in the early stages of experimental canine osteoarthritis (OA). Native PG aggregates are not saturated with link protein and the molar ration link protein: PG monomer obtained in native aggregates is lower than that observed for the whole cartilage matrix. These observations suggest that link protein might have other functions than those related to PG aggregation. The smaller aggregates are concentrated in the superficial layers of articular cartilage whereas the larger aggregates are concentrated in the middle and deep layers. Although these differences in the topographical distribution of aggregates reflect topographical changes in the metabolic activity of chondrocytes, it has not yet been clearly established whether these metabolic changes are inherent to the cells or secondary to dissimilar physio-chemical and/or mechanical factors in the different cartilage layers. The topographical variations in the distribution of both aggregates also suggest that the two types of aggregates may have different functions. The large and link-rich aggregates might play an important role in the material properties of cartilage since they dramatically increase the rheological properties of PGs and they are larger and more abundant in areas of maximum than of minimum contact. On the other hand, the formation of the large ahhregates probably allows the cells to achieve an optimal concentration of PGs in the different topographical areas of cartilage matric since with degree of physiological stress and with tissue depth from the articular surface there is a strong correlation between the total PG content and the relative size and abundance of the large aggregates. How is this achieved is however not clear. The relevance of the large aggregates is further compounded by their disappearance in the early stages of osteoarthritis (OA). This event could contribute significantly to the biochemical and biomechanical alterations of OA cartilage. We do not have any clear explanation for this important phenomenon but we provide indirect evidence that an alteration in link protein synthesis and/or link incorporation into aggregates might be relevant. Another important event in OA is the progressive reduction in the tissue content of HA, although the HA molecules remaining in the tissue are apparently not degraded. On the other hand, there is also a progressive increase in the tissue content of proteinases which contribute to the degradation of cartilage. As several of these enzymes can cleave PGs in the interglobular domain, the G1 domain remains anchored on the matrix whereas the CS-bearing domain, which provides the main physical properties of PGs, can diffuse out the tissue. The accumulation of G1 domains within OA matrix might interfere with the aggravation of newly synthesized PGs. In OA tissue there is an imbalance between proteinases and their inhibitor(s). However neither the factors responsible for such imbalance nor the prime movers of proteinase activation have been clerly established. Complex interactions between the networks of cytokines and the network of growth factors might be relevant but require further investigations. Despite the increase in their catabolic activities chondrocytes also exhibits an increase in their anabolic activities. This might explain at least in part why OA develops slowly. The differences in metabolic activities between normal and OA chondrocytes persist in vivo. Whether these alterations represent a primary change or develop after the cells are stimulated by OA initiating factors in unknown. Interestingly, the progressive changes in the size distribution of PG aggregates in OA are quite similar to those observed in the growth plate during enchodral calcification although they occur at a quite lower pace in the disease process than in the physiological process. This observation together with the finding of type X collagen in OA chondrocytes might progressively become hypertrophicThèse d'agrégation de l'enseignement supérieur -- UCL, 199

Serum Levels of β2-Microglobulin in Crohn's Disease

To the Editor: In view of our interest in serum levels of β2-microglobulin as a measure of activity in autoimmune disease,1 ,2 we would like to comment on the discrepancies between the data of Descos et al.3 and Kruis et al.4 on β2-microglobulin levels in Crohn's disease. We studied serum levels and urinary excretion of β2-microglobulin (Phadebas RIA Kits) in 23 patients with Crohn's disease. Patients were 27 to 56 years of age, and none had received corticoids, azathioprine, or levamisole. Six had ileitis, 12 ileocolitis, and five colitis. According to Best's criteria,5 the disease. © 1980, Massachusetts Medical Society. All rights reserved.SCOPUS: le.jinfo:eu-repo/semantics/publishe

Les marqueurs biologiques de l'arthrose

The degradation of proteoglycans, collagens and proteins in the articular cartilage matrix produces fragments which diffuse out of the tissue and into the joint fluid. These fragments subsequently appear in the blood circulation and are eventually eliminated by the liver or the kidney. Recent studies have shown that the joint fluid and blood levels of these biological markers of degradation can be used to monitor abnormal metabolic processes in cartilages. The joint fluid level of a cartilage-derived marker provides information about the metabolism of that molecule in that joint. In blood, levels of specific markers have been shown to be helpful in identifying systemic changes affecting the metabolism of matrix constituents in all or most cartilages in the body. Measurement of different biological markers in body fluids have proved useful in identifying increased catabolic activities in articular cartilage during the preradiological stages of osteoarthritis. These markers have great potential for monitoring disease activity, assessing disease progression, examining responses to drug therapy and evaluating long-term prognosis. In addition, markers should prove most useful in prospective studies at identifying early changes in cartilage metabolism in humans at high risk of developing post-traumatic osteoarthritis