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At least 19 recordsLinked to original sources

Synostosis of joints caused by mutant FBN2 is linked to the abnormalities and misdifferentiation of articular surface cells.

PURPOSE: FBN2, a high-confidence effector gene for osteoarthritis (OA), was investigated for its potential role in synostosis of joints (SJ) because several OA-related genes are known to cause SJ. METHODS: We analyzed variants in OA-related genes using exome sequencing data from Chinese-Han participants with radioulnar synostosis (RUS). Variants were classified following American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Fbn2 knockout mice were generated via CRISPR/Cas9 and evaluated through radiological and histopathological analyses at multiple developmental stages, with complementary cellular and molecular studies. RESULTS: We identified 15 rare, damaging FBN2 variants in unrelated RUS families, including 7 likely pathogenic variants (4 null variants). Fbn2 knockout mice (both homozygous and heterozygous) exhibited SJ phenotypes. Unlike previously reported SJ mechanisms involving failed interzone formation, Fbn2-related SJ occurred after normal interzone formation. Mutant mice showed significant alterations in extracellular matrix composition and volume within articular surface cells. We proposed that these extracellular matrix changes mediated the transdifferentiation of articular surface cells into osteoblasts, which ultimately developed into bones over time. CONCLUSION: We identified FBN2 pathogenic variants that caused SJ in humans and mice. SJ caused by mutant FBN2 is linked to the abnormalities and misdifferentiation of articular surface cells.

Fibrillin-2

Interaction of polymorphonuclear leukocytes with immune complexes trapped in joint collagenous tissues.

The present experiments were designed to investigate in vitro interactions between polymorphonuclear leukocytes (PMN) and rabbit joint collagenous tissues containing trapped immune complexes. Articular cartilages and menisci from antigen-injected and control joints were incubated with normal PMN isolated from rabbit peritoneal exudates or blood. After incubation of cartilage and menisci from antigen-injected joints with PMN, large numbers of PMN became attached to the articular surface. In areas of superficial erosion, the PMN invaded the tissue several cell diameters below the articular surface. Through immunoelectron microscopy, degranulated PMN were observed in scattered areas to phagocytose amorphous material containing rabbit Ig. Following addition of PMN to control tissues, only a few PMN became attached to the articular surface. When tissues from monosodium urate-injected joints were incubated with PMN, these cells were found attached to the surface in moderate numbers, but invasion into the tissues was not seen. These studies indicate that immune complexes trapped in joint collagenous tissues may lead to enhanced release of lysosomal hydrolases.

Animals

Studies on cartilage formation XXL Activity of enzymes belonging to the pentose-phosphate cycle in the regenerating articular surface.

The distal articular surface of the femur was removed operatively in 36 dogs. In the regenerating chondrifying articular surface and in the granulation tissue adhering to the capsule glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were determined 7, 33 and 70 days after operation. In both tissues the activity of these enzymes characteristic of the pentose phosphate cycle ws the highest in the early postoperative stage. This initial increase in activity was followed by a marked reduction in the regenerating articular surface and by a moderate decrease in the tissue adhering to the capsule. For the loss in activity occurring in the chondrifying articular surface, the connective tissue cells (fibroblasts) are responsible. Cartilage precursors and young chondrocytes show a high glucose-6-phosphate dehydrogenase and 6-phosphogluconate activity. Presumably, in the given case of the functions of the pentose-phosphate cycle the NADPH generation and supply of building stones prevail. The activity of these enzymes ws determined in the articular cartilage and in the synovial membrane of the knee joint in further 18 dogs. The activity in the articular cartilage was very slight as compared to that in the synovial membrane.

Animals

Studies on cartilage formation. XX. Histochemical investigation of some enzymes of glycogen metabolsim in regenerative articular surfaces.

In 28 dogs the distal articular cartilage of the femur was removed and the regenerating articular surface on the 70th postoperative day was studied histochemically for hexokinase, glucose-6-phosphatase, phosphohexose-isomerase, fructose-1, 6-diphosphatase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, lactate dehydrogenase isoenzymes, phosphoglucomutase, phosphorylase, glycogen synthetase, UDP--glucose dehydrogenase, and UDP-glucuronic acid-4-epimerase. The articular surface consisted of fibrous tissue and of cartilage islets. The latter contained cells differentiating into cartilage and young chondrocytes. The glycolytic enzymes reacted positively in the regenerative articular surface. Enzyme activities were higher in the cells (particularly the chondroblasts and young chondrocytes) of the cartilage islets than in the connective tissue. In the cells differentiations into cartilage, beside the LDH isoenzymes characteristic of glycolysis, a significant LDH1 and LDH2 activity was observed. At the same site the presence of fructose-1, 6-diphosphatase-activity could be assumed, but there was no glucose-6-phosphatase activity. Glycogen synthesis proceeded in the cells of the cartilage islets and UDP-glucuronic acid-4-epimerase activity was observed in the differentiated cells. UDP-glucose dehydrogenase activity was positive in every section of the articular surface.

Animals

[Scanning electron microscopy study of the synovial membrane in rheumatoid arthritis].

A comparative study under the scanning electron microscope of rheumatoid synovial membranes, 5 arthrosic synovial membranes, one tuberculous membrane, and 3 normal synovial membranes showed the pathological changes in the synovial membrane due to rheumatoid arthritis: Inflammatory aspect of the synovial fringes, surrounded by turgid and proliferative villous processes. Granular appearance of the endo-articular surface like a "pebble beach". Dome-shaped synoviocyte layer, standing out well above the subjacent intimal layer, associated with small round cells, also with a raised margin, covering most of the endo-articular surface. Plasma membrane of the superficial synovial cells, covered with numerous and various differentiations and abundant microvillous processes. Reticular deposits or layers, covering the apical poles of the synoviocytes.

Arthritis, Rheumatoid

In vitro collagen biosynthesis in healing and normal rabbit articular cartilage.

To examine the repair collagens produced by cells in injured cartilage, the femoral articular surfaces of three groups of New Zealand white rabbits were injured by making both superficial and deep lacerations and drill holes. Eight weeks after surgery, the rabbits were killed and slices of injured articular cartilage were harvested. The types of collagen being synthesized at the site of these lesions were identified by labeling the recovered specimens in vitro with 3H-proline and by characterizing the collagen using sodium dodecyl sulphate electrophoresis, carboxymethyl cellulose chromatography, and cyanogen bromide peptide analysis. In all cases, tissue-specific type II ([alpha1 (II)]3) cartilage collagen was synthesized. Histological examination using toluidine blue showed that the chondrocytes bordering the cartilage defect produced by deep lacerations and drill holes responded by increased cellular activity, as shown by cell cloning and increased matrix staining. The drilled holes were completely filled by tissue with staining and morphological characteristics similar to those of hyaline cartilage.

Animals

Giant cell synovitis associated with failed polyethylene patellar replacements.

Destroyed patellar articular surfaces were replaced with a high molecular weight polyethylene prosthesis in two patients. The patellofemoral articulation of the femur consisted of eburnated bone in one case and degenerative cartilage in the other. Both operations failed within one year because of a giant cell synovitis caused by a high volume (0.2 cc) of fine polyethylene (1-100 mu) wear particles. Ultra high molecular weight polyethylene should not be used as a prosthetic bearing surface to articulate against cortical, cancellous or eburnated bone or against degenerative articular cartilage in a major joint.

Aged

[Structure and function of the external part of the articular cartilage].

The data on electron microscopic studies of the main structural elements of the superficial layer of the articular cartilage are represented. The articular cartilage of the femoral lead in young rabbits has been studied. The articular cartilage has no ideal smooth surface but three are some pressings of different sizes. The most superficial cartilage layer--cell-free zone--consists of collagene fibers and hyaluronic fibrils which are closely connected with the ground substance of the cartilage. Superficial chondrocytes are mature, differentiated but functionally weakly active cells. Under normal conditions, destruction (obliteration) of the cell-free zone and desquamation of superficial cells are impossible.

Animals

Articular cartilage degradation and the pathology of haemophilic arthropathy.

Synovial membrane and specimens of articular cartilage, obtained from the affected knee joints of 5 haemophilic patients at the time of surgical synovectomy, were studied. All the synovial specimens showed villous proliferation and multiplication of synovial cells. Haemosiderin granules were present within synovial cells and in macrophages. There was congestion and capillary proliferation. An inflammatory infiltrate of plasma cells and lymphocytes was seen in some instances. Articular cartilage changes were classified into the following 4 grades according to severity: 1--an increase in the number of surface chondrocytes with fibrous metaplasia, and the appearance of superficial fissures; 2--a fibrous vascularized overgrowth, resembling rheumatoid pannus; 3--deep fissuring and necrosis of cartilage; 4--erosion and disappearance of articular cartilage with exposure of subchondral bone. In the first 3 grades, deep nests of chondrocytes containing haemosiderin were present. These cell aggregates became larger and more degenerate as cartilage degradation progressed. Damaged articular cartilage was deficient in glycosaminoglycan (acid mucopolysaccharide). No excess enzyme activity could be demonstrated within the cartilage matrix. Immunofluorescent studies were not helpful. Electron microscopical examination revealed siderosomes within degenerate chondrocytes and synovial cells. Granules resembling haemosiderin were also present in the cartilage matrix. It is considered that iron products affect both chondrocytes and matrix adversely and play a part in articular cartilage destruction in haemophilia.

Adolescent

Atypical ossicle joint lesions in rheumatoid arthritis with sicca syndrome (Sjögren syndrome).

Atypical incudomalleal and incudostapedial joint changes were found in a 55-year-old woman with long-standing rheumatoid arthritis and sicca syndrome (Sjögren syndrome). Available audiograms taken at 37 and 42 years of age demonstrated slight bilateral high-frequency loss of hearing. The ossicular joint changes involved dissolution of disk material together with proliferation of synovial-type elements of the disk and articular surfaces, with formation of pannus-like tissue. There was extensive destruction of cartilage, with cellular collagenous tissue extending along the exposed bone surfaces. Despite strong similarities to rheumatoid arthritis, a definite diagnosis cannot be made in the absence of the inflammatory, lymphocyteplasma cell component.

Arthritis, Rheumatoid

[The treatment of diaphyso-epiphyseal tumours by local resection with the preservation of joint movement. A report of four cases (author's transl)].

Four cases of epiphyseal tumours were treated by the authors by local resection. In two cases, there was a giant-cell tumour of the lower end of the femur, in one case a giant-cell tumour of the lower end of the radius and in one case a juxta-cortical sarcoma of the lower end of the radius. In the two cases involving the knees, resection preserved the articular surface and the subchondral bone. Reconstruction was achieved by a cortical autograft. In all cases, painless joint movement was preserved with satisfactory muscle power.

Adult

The proliferation of chondrocytes and pannus in adjuvant arthritis.

Cell proliferation in the pannus formation of adjuvant arthritis was studied by autoradiography. It was found that after day 9 an increased cell proliferation starts in the joint capsule recessus and synovial villi on the injected side. From these proliferating cells a pannus, which during the first phase frequently consists only of few cell layers, extends over the cartilage surface. With advancing disease the thickness of the pannus increases and further centripetal growth may cause the entire cartilage surface to be covered. This proliferating pannus tissue may invade the cartilage and destroy it. Since in this area of destruction labelled cells are frequently present, it may be assumed that proliferating cells with a high enzyme content are particularly responsible for the immediate degradation of cartilage. No involvement of chondrocytes in pannus formation was confirmed by the methods employed. There was neither increased proliferation of surface chondrocytes nor increased proliferation of chondrocytes in the depth of cartilage.

Animals

[The cellularity of fibrillated articular cartilage. A comparative study of age-related and osteoarthrotic cartilage lesions from the human femoral head].

The cellularity of human femoral head cartilage has been studied in age-related and osteoarthrotic fibrillated samples and control intact samples. Age-related fibrillated cartilage shows a marked increase of the cell density which is directly related to the proliferation of cell clusters and to cartilage thinning. In osteoarthrotic cartilage lesions multicellular clusters are less frequent and cell density is decreased. A smooth aspect of the exposed cartilage surface and an increased subchondral bone mass are only found in osteoar/hrotic samples. The findings suggest that age-related and osteoarthrotic cartilage lesions are due to different mechanical stresses governing the cellularity of the tissue.

Aging

Enhancement of healing in osteochondral defects by collagen sponge implants.

Implants of porous, highly cross-linked collagen sponge (CS) were tested for their capacity to enhance the healing of osteochondral defects in rabbits. Comparison was made to the healing of similar defects with polyvinyl alcohol sponge (PVAS) implants and with no implants (CONT). Evaluation was carried out up to 44 weeks following implantation and included observation of host cellular response, biodegradability of implant, gross appearance of restored joint surface, collagenous architecture of repair tissue, and properties of the junctions of implants and host articular cartilage, subchondral bone, and medullary bone. Collagen sponge proved most effective in promoting healing of osteochondral defects with fibrous and fibrocartilaginous tissue over restored subchondral bone. Collagen sponge showed many desirable properties as a potential material for biologic resurfacing of damaged joints. These properties included porosity, biodegradability, biocompatability, ability to mechanically protect cells and matrix while directing cell ingrowth, and an available chemical technology for modifying its biomechanical and biological properties. Comparative analysis of results of healing of CS, PVAS, and CONT osteochondral defects suggest rational design criteria for implant materials to improve their effectiveness in restoration of articular surfaces.

Animals

Isolated epiphyseal chondrocyte allografts into joint surfaces. An experimental study in rabbits.

Isolated epiphyseal chondrocytes from 5 week old female New Zealand white rabbits were transplanted as allografts into drill holes in the tibial articular surface of adult male New Zealand white rabbits. The grafts were examined after 8 weeks. Fresh chondrocytes which were partially separated from their matrix were more successful (47%) than completely separated cells (20%) and were significantly more successful (P greater than 0.05) in skeletally mature (58%) as opposed to immature recipients (20%). Storage of the cells at -79 degrees C for 2 to 9 days or at -196 degrees C for 36 to 58 weeks gave successful results of 23% and 33%, respectively. Control defects showed fibrocartilage filling the defect in 25%. The factors affecting survival of chondrocyte allografts require further study before clinical application of the method.

Animals

Studies on cathepsin B in human articular cartilage.

The thiol proteinase cathepsin B (EC 3.4.22.1), previously called cathepsin B1, was assayed in human articular cartilage by its hydrolysis of the synthetic substrate alpha-N-benzoyl-DL-arginine 2-naphthylamide. The enzyme was activated by cysteine and EDTA and completely inhibited by iodoacetamide and HgCl2. It was also partially inhibited by whole human serum. Human osteoarthrotic cartilage had increased activity when compared with normal cartilage. Cathepsin B activity of normal cartilage was age-related, being high in juveniles and declining to low values in adult and elderly individuals. Cathepsin D and cathepsin B both exhibited a zonal variation through the cartilage depth; the surface cells appeared to contain more activity than those close to the subchondral bone.

Adolescent

Synovial pathology in Behcet's syndrome.

Eight specimens of synovial membrane from 6 patients with 'definite' Behcet's syndrome were available for histological examination. Only the superficial zones of the synovia were affected, all except one being replaced by dense inflamed granulation tissue composed of lymphocytes mingled with macrophages, vascular elements, fibroblasts, and neutrophils. There was a marked plasma cell infiltrate and lymphoid follicle formation in one synovium only, and there was no evidence of infection. Pannus and erosive change were present in the three specimens which included the articular surface, the erosive change being visualised radiologically in two of these. It is suggested that these appearances are characteristic of Behcet's syndrome and should be added to the list of diagnostic criteria.

Adult

[Study of articular cartilage in arthrosis. Histological and biochemical data].

Arthrosis is characterized by destructive lesions of cartilage occuring in the pressure areas of the articular surfaces and leading to the denudation and erosion of the sub-chondral bone. At a further stage these lesions are distinguished from cartilage lesions due to aging and correspond to the progressive erosion of a tissue whose cells present mainly signs of degeneration and whose tissue contains few proteoglycans. The histologic appearance of the initial lesions of the cartilage remains a matter of controversy and ambiguity. Some look like fissures in relatively healthy tissues where the cells show signs of proliferation and hyperactivity. Others correspond to the fragmentation of tissues whose cells and connective tissues are severely damaged. The first biochemical changes of cartilage in arthrosis associate a disorder of proteoglycan aggregation and an increase in the water content. The modifications of proteoglycans could be due to the action of proteolytic enzymes or to a lack of synthesis due to changes in chondrocyte glycotransferase. The biochemical changes could be the cause of cartilage destruction following pressures, since they can decrease the resistance of the tissue. They could nevertheless, be secondary to rupture lesions of the collagen, due only to stress. Arthrosis can then be secondary to either a special weakness of the cartilage or abnormal stress factors.

Arthritis