Synovial chondromatosis of the pisotriquetral joint with secondary osteoarthritis: case report

There are only a few reported cases of synovial chondromatosis affecting pisotriquetral joint (PT). Osteoarthritis of the PT is also rare and can be as disabling as osteoarthritis of any other joint. We report this to be the unique case of synovial chondromatosis of the PT joint with secondary osteoarthritis.     

CCN3-mediated promotion of sulfated proteoglycan synthesis in rat chondrocytes from developing joint heads

Chondrocytes forming articular cartilage are embedded in a vast amount of extracellular matrix having physical stiffness and elasticity, properties that support the mechanical load from bones and enable the flexible movement of synovial joints. Unlike chondrocytes that conduct the growth of long bones by forming the growth plate, articular chondrocytes show suppressed cell proliferation, unless these cells are exposed to pathological conditions such as mechanical overload. In the present study, we found that one of the members of the CCN family, CCN3, was significantly expressed in chondrocytes isolated from the epiphyseal head in developing rat synovial joints. Evaluation of the effect of recombinant CCN3 on those chondrocytes revealed that CCN3 promoted proteoglycan synthesis, whereas this factor repressed the proliferation of the same cells. These results suggest a critical role for CCN3 in the regulation of the biological properties of articular chondrocytes.     

Bone morphogenetic proteins are involved in the pathobiology of synovial chondromatosis

Synovial chondromatosis is characterized by the formation of osteocartilaginous nodules (free bodies) under the surface of the synovial membrane in joints. Free bodies and synovium isolated from synovial chondromatosis patients expressed high levels of BMP-2 and BMP-4 mRNAs. BMP-2 stimulated the expression of Sox9, Col2a1, and Aggrecan mRNAs in free-body and synovial cells and that of Runx2, Col1a1, and Osteocalcin mRNAs in the free-body cells only. BMP-2 increased the number of alcian blue-positive colonies in the free-body cell culture but not in the synovial cell culture. Noggin suppressed the expression of Sox9, Col2a1, Aggrecan, and Runx2 mRNAs in both the free-body and synovial cells. Further, it inhibited Osteocalcin expression in the synovial cells. These results suggest that BMPs are involved in the pathobiology of cartilaginous and osteogenic metaplasia observed in synovial chondromatosis.     

The influence of the acetabular labrum seal,intact articular superficial zone and synovial fluid thixotropy on squeeze-film lubrication of a spherical synovial joint

A model of synovial fluid (SF) filtration by articular cartilage (AC) in a step-loaded spherical synovial joint at rest is presented. The effects of joint pathology (such as a depleted acetabular labrum, a depleted cartilage superficial zone consistent with early osteoarthritis and an inflammatory SF) on the squeezed synovial film are also investigated. Biphasic mixture models for AC (ideal fluid and elastic porous transversely isotropic two-layer matrix) and for SF (ideal and thixotropic fluids) are applied and the following results are obtained. If the acetabular labrum is able to seal the pressurised SF between the articular surfaces (as in the normal hip joint), the fluid in the synovial film and in the cartilage within the labral ring is homogeneously pressurised. The articular surfaces remain separated by a fluid film for minutes. If the labrum is destroyed or absent and the SF can escape across the contact edge, the fluid pressure is non-homogeneous and with a small jump at the articular surface at the very moment of load application. The ensuing synovial film filtration by porous cartilage is lower for the normal cartilage (with the intact superficial zone) than if this zone is already depleted or rubbed off as in the early stage of primary osteoarthritis. Compared with the inflammatory (Newtonian) SF, the normal (thixotropic) fluid applies favourably in the squeezed film near the contact centre only, yielding a thicker SF film there, but not affecting the minimum thickness in the fluid film profile at a fixed time. For all that, in the unsealed case for both the normal and pathological joint, the macromolecular concentration of the hyaluronic acid-protein complex in the synovial film quickly increases due to the filtration in the greater part of the contact. A stable synovial gel film, thick on the order of 10(-7)m, protecting the articular surfaces from the intimate contact, is formed within a couple of seconds. Boundary lubrication by the synovial gel is established if sliding motion follows until a fresh SF is entrained into the contact. This theoretical prediction is open for experimental verifications.     

The occurrence of hydroxyapatite crystals in extracellular matrix vesicles after surgical manipulation of the rabbit knee joint

Summary Free autologous grafts of synovial tissue were transplanted into experimental defects produced in the articular cartilage of rabbit knee joints. The grafted tissue underwent transformation into fibrocartilage. Extracellular matrix vesicles associated with calcified areas were present at the grafted sites. Hydroxyapatite crystals were found within these vesicles and in their vicinity. No calcification occurred in articular cartilage from sham operated joints in which defects were produced but no grafts made and in normal controls. These tissues showed abundant matrix vesicles devoid of crystalline mineral. A careful study of normal synovial tissue did not reveal matrix vesicles and calcifications. The present observations suggest that matrix vesicles in normal articular cartilage exist in a latent form. Vesicle mineralization following surgical manipulations of the joint is probably a manifestation of the metabolic stage of the tissue.     

Comparative assessment of articular cartilage and synovial membrane in experimental haemarthrosis

The changes in articular cartilage and synovial membrane of the knee joints were studied in two groups of rabbits and Wistar rats with experimental haemarthrosis, electron microscopically. Hamarthrosis was produced in group 1 by a single autologous blood injection, in group 2 by intraarticular fracture of the femoral condyles. Samples were taken from the intact articular cartilage, the menisci and the infrapatellar portion of the synovial membrane 12 h to 20 days after intervention. Blood resorption occurs only in the synovial membrane. Fragmentation of erythrocytes and erythrocytophagy by synovial macrophages is documented. The different stages of intracellular digestion of erythrocyte fragments are traced down. Synovial fibroblasts do not participate in erythrocytophagy, although they disclose morphological signs of enhanced functional activity. The findings show changes in the matrix and chondrocytes within the articular cartilage and menisci, and presence of free erythrocytes and lipoprotein complexes amidst the collagen fibres of the matrix. The chondrocytes are poor in cell organelles, while the intracytoplasmic filaments, lipid droplets and glycogen granules are augmented in number. There is no evidence of erythrocytophagy by cartilage cells. On single blood injection in the joint, the ensuing changes are reversible, and the normal synovial membrane structure is restored much quicker than the articular cartilage.     

Cerebral and ocular abnormalities with anterior pituitary insufficiency of familial nature

Three families presenting one or several cases of brain or ophthalmic abnormalities and an hypopituitarism at least by one of the members have been observed. In the first family, the mother and one of her sons present bilateral choroidoretineal coloboma with amblyopia; one of these two suffers as well from panhypopituitarism. In the second family two premature twins, a brother and his sister, present a syndrome with hypophyseal dwarfism and ophthalmic abnormalities, consisting in the boy's case in an peripapillary depigmentation with no visible sight trouble whereas girl's is showing an extreme microphthalmia with major mental retardation. In the third family two 2nd degree cousins present a panhypopituitarism but only one of the two reveals through neuroradiological investigations corpus callosum and septum lucidum agenesia. The karyotype is normal in all the cases. An hereditary mechanism appears clearly in the first family. It is possible in the second, probable in the third one.     

Temporospatial expression of tissue inhibitors of matrix metalloproteinases-1, -2 and -3 during development, growth and aging of the mouse skeleton

Proteolytic degradation of collagen-rich extracellular matrices is a key feature in the development, growth and aging of skeleton. Matrix metalloproteinases (MMPs) are a family of enzymes capable of performing this function, whereas tissue inhibitors of MMPs (TIMPs) are believed to play an important role in regulating their activity. To better understand the roles of TIMP-1, -2 and -3, we have studied their mRNA levels in several different mouse tissues with special emphasis on the skeleton and the developing eye. A systematic analysis of TIMP-1, -2 and -3 mRNA levels in mouse knee joints during growth and aging demonstrated markedly different expression patterns for each TIMP. Immunohistochemical analysis revealed several time-dependent changes in the distribution of TIMP-1 and -2 in articular and growth cartilages, synovial tissue and bone. The data suggest that upon aging synovial tissue becomes the major source of synovial fluid TIMPs. In articular cartilage these inhibitors were mainly found in the deep layer and in subchondral bone. Compared with epiphyseal growth plate, the amounts of TIMP-1 and -2 in articular cartilage were quite low. These findings suggest that the capacity of articular cartilage chondrocytes to inhibit MMP activities by local production of TIMPs is limited, which may be of consequence during osteoarthritic cartilage degeneration.     

PNMA family: Protein interaction network and cell signalling pathways implicated in cancer and apoptosis

Paraneoplastic Ma Family (PNMA) comprises a growing number of family members which share relatively conserved protein sequences encoded by the human genome and is localized to several human chromosomes, including the X-chromosome. Based on sequence analysis, PNMA family members share sequence homology to the Gag protein of LTR retrotransposon, and several family members with aberrant protein expressions have been reported to be closely associated with the human Paraneoplastic Disorder (PND). In addition, gene mutations of specific members of PNMA family are known to be associated with human mental retardation or 3-M syndrome consisting of restrictive post-natal growth or dwarfism, and development of skeletal abnormalities. Other than sequence homology, the physiological function of many members in this family remains unclear. However, several members of this family have been characterized, including cell signalling events mediated by these proteins that are associated with apoptosis, and cancer in different cell types. Furthermore, while certain PNMA family members show restricted gene expression in the human brain and testis, other PNMA family members exhibit broader gene expression or preferential and selective protein interaction profiles, suggesting functional divergence within the family. Functional analysis of some members of this family have identified protein domains that are required for subcellular localization, protein-protein interactions, and cell signalling events which are the focus of this review paper.     

LDH and LDH Isoenzymes of Synovial Fluid in the Horse

LDH is an intracellular enzyme, which when cells degenerate is released to the extracellular spaces and body fluids. Cells and organs in the mammalian body differ from each other with respect to their LDH isoenzyme patterns. These circumstances have led to the use of LDH isoenzyme determinations in laboratory diagnostic work. In the present investigation total LDH activity and LDH isoenzyme distribution in equine synovial fluid from healthy joints, joints with serous arthritis, osteochondrosis dissecans and arthrosis, were determined. The fluids from the diseased joints differed from normal synovial fluid with respect to total LDH activity, and the different joint diseases each seemed to give rise to a characteristic isoenzyme pattern. In order to examine possible sources of the increased LDH activity and altered isoenzyme patterns, blood plasma, red and white blood cells, synovial membrane and articular cartilage were also studied. It was found that LDH4 and LDH5 were present in high amounts in articular cartilage, and an increase in these isoenzymes was the most characteristic feature in synovial fluid from joints with arthrosis. The results were discussed in view of possible diagnostic value of isoenzyme determinations on synovial fluid.     

Identification of link proteins in canine synovial cell cultures and canine articular cartilage

Link proteins are glycoproteins in cartilage that are involved in the stabilization of aggregates of proteoglycans and hyaluronic acid. We have identified link proteins in synovial cell cultures form normal canine synovium using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunofluorescence, and immunolocation with specific antibodies by electrophoretic transfer. We have also found evidence for the synthesis of link proteins in these cultures by fluorography of radiolabeled synovial cell extracts. We have identified a 70,000 mol-wt protein in canine synovial cell culture extracts that has antigenic cross-reactivity with the 48,000-mol-wt link protein. Three link proteins were identified in normal canine articular cartilage. These results indicate that link proteins are more widely distributed in connective tissues than previously recognized and may have biological functions other than aggregate stabilization.     

Effects of nitric oxide on matrix metalloproteinase-2 production by rheumatoid synovial cells

Nitric oxide (NO) is a multifunctional messenger molecule generated from L-arginine by a family of enzymes, including nitric oxide synthase (NOS). This study was performed to examine whether NO modulates the production of matrix metalloproteinases (MMPs), which degrade all components of extracellular matrix (ECM), in rheumatoid synovial cells. We investigated the effects of exogenously generated NO by a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the MMPs production by rheumatoid synovial cells. Culture media conditioned by SNAP-treated synovial cells were examined by gelatin zymography and immunoblot analysis. Incubation of synovial cells with SNAP resulted in gelatinase A production in a dose-dependent fashion. Furthermore, RT-PCR analysis demonstrated that MMP-2 mRNA expression was induced in SNAP-treated synovial cells. In contrast, SNAP did not influence the production of TIMP-1 and TIMP-2, which preferentially inhibit MMP-2, by rheumatoid synovial cells. Our data indicate that NO could modulate MMP production by rheumatoid synovial cells and therefore contribute to ECM degradation of articular components in RA.     

Squeeze-film lubrication of the human ankle joint with synovial fluid filtrated by articular cartilage with the superficial zone worn out

A squeeze-film lubrication model of the human ankle joint in standing that takes into account the fluid transport across the articular surface is presented. Articular cartilage is a biphasic mixture of the ideal interstitial fluid and an elastic permeable isotropic homogeneous intrinsically incompressible matrix. The simple homogeneous model for articular cartilage models the case of early osteoarthritis, when the intact superficial zone of the normal articular cartilage, much stiffer in tension than the bulk material, has been already disrupted or worn out. The calculations indicate for this case that in normal approach motion the lubricating fluid film is quickly depleted and turned into a synovial gel film that is supposed to serve as a boundary lubricant if sliding motion follows     

Induction of collagenase mRNA in lapine articular chondrocytes by synovial factors and interleukin-1

The cDNA probe H-9, originally constructed to recognize a portion of the mRNA for lapine synovial collagenase, also hybridized with a RNA of the same size (approximately 2.0 kb) isolated from activated lapine articular chondrocytes. Primary, monolayer cultures of lapine articular chondrocytes did not contain detectable amounts of this RNA, nor did they secrete measurable amounts of collagenase into their culture media. Following exposure to synovial factors, the chondrocytes contained high levels of collagenase mRNA, while their conditioned media had considerable collagenolytic activity. Collagenase mRNA started to appear in chondrocytes 3-5 h after treatment with the synovial material. Maximum levels occurred after 12-24 h. Recombinant human interleukin-1 also induced the appearance of this mRNA. We conclude that chondrocyte collagenase is likely to be the same gene product as synovial collagenase, and that its regulation by lapine articular chondrocytes probably occurs at a pretranslational level.     

Spezifische aberration eines chromosoms der C-gruppe bei mehreren mitgliedern einer sippe

Zusammenfassung Bei einer Chromosomenanalyse an Lymphocyten eines 15jährigen Patienten wurde in 26,6% der untersuchten Zellen eine spezifische Aberration eines C-Chromosoms, wahrscheinlich des Chromosoms 10, beobachtet. Weitere 7 Familienmitglieder des Probanden wurden ebenfalls chromosomal untersucht, und bei 3 von ihnen konnte in unterschiedlichen Prozentsätzen dieselbe Anomalie festgestellt werden. Bis auf den Probanden (Minderwuchs) sind alle Träger dieser Anomalie als klinisch normal zu bezeichnen.

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Familiar apprearence of a C-chromosome aberration

Summary A specific chromosomal aberration of one of the C-chromosomes (probably chromosome 10) was found in 26.6 per cent of all cultured lymphocytes of a 15 year old boy. Among 7 members of his family 3 had the same aberration with different frequencies. With the exception of the proband (dwarfism) there were no striking abnormalities present in affected members of his family.

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Herrn Prof. Dr. Dr. F. Mainx in herzlicher Dankbarkeit gewidmet.     

The thixotropic effect of the synovial fluid in squeeze-film lubrication of the human hip joint.

The thixotropic (shear-thinning) effect of the synovial fluid in squeeze-film lubrication of the human hip joint is evaluated, taking into account filtration of the squeezed synovial film by biphasic articular cartilage. A porous, homogeneous, elastic cartilage matrix filled with the interstitial ideal fluid, with the intact superficial zone (of lower permeability and stiffness in compression) already disrupted or worn away, models an early stage of arthritis. Due to a high viscosity of the normal synovial fluid at very low shear rates, the squeezed synovial film at a fixed time after the application of a steady load is found to be much thicker in a small central part of the lubricated contact area. In the remaining part, the film is thin as it corresponds to the Newtonian fluid with the same high-shear-rate viscosity. Filtration is lower for the normal cartilage with the intact superficial zone due to its lower permeability and compression stiffness. But even in the fictitious case of zero filtration, calculations show that the effect of thixotropy on the increase of the minimum synovial film thickness would manifest itself as late as after several tens of seconds since the physiologic load application. At that time, this thickness would be as low as about 0.3 microm. It follows that thixotropy of the normal synovial fluid (and so much more of the inflammatory fluid) is irrelevant in squeeze-film lubrication of both the normal and arthritic human hip joints.     

Vasculature of the normal and arthritic synovial joint

The vasculature of the normal and arthritic knee is described. The joint contains a number of different tissues, many of which are heterogeneous and each with varying degrees of vascularization. In the normal joint the vasculature is highly organised, some tissues are highly vascular with well defined vascular organisation, whilst other tissues are avascular. During arthritis vascular turnover is increased. This vascular plasticity leads to redistribution of the vascular bed and may compromise its functional ability. The normal joint is able to regulate its blood flow, but this ability may be compromised by the inflammation and increased synovial fluid volume that are associated with joint disease. Growth of the subchondral vasculature into the articular cartilage may also occur, leading to ossification of the articular cartilage.     

Distribution of immunoreactive fibronectin and collagen (type I, III, IV) in mouse joints. Fibronectin, an essential component of the synovial cavity border

Hyaluronic acid traditionally has been held to play a major role in the control of transsynovial exchanges and in the biomechanical properties of synovial fluid and cartilage surfaces. As with previous ultrastructural observations, immunohistochemical data show that a more complex differentiation must be envisaged for interstitial tissues bordering the synovial cavity. In particular, the elective concentration of fibronectin in the lining layer of the synovial membrane and its presence as a fine layer at the articular cartilage surfaces indicate that this glycoprotein, along with hyaluronic acid, may play an important role in joint physiology. Only immunoreactivity for type III procollagen is diffusely distributed in the entire synovial membrane and, in addition, is found associated with fibronectin immunoreactivity at the articular cartilage surfaces.     

Synovial chondromatosis in raptors

Fourteen raptors, consisting of 13 great horned owls (Bubo virginianus) and one red-tailed hawk (Buteo jamaicensis), from central and north central Minnesota, western Wisconsin, and eastern South Dakota (USA) were admitted to a raptor rehabilitation center between June 1992 and June 1995, with perisynovial and synovial chondromatosis affecting multiple joints. Birds were severely debilitated primarily due to loss of shoulder motion. The etiology of these lesions in raptors is unknown.