Chondrocyte-mediated collagenolysis correlates with cartilage destruction grades in osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is associated with destruction of type II collagen-rich hyaline articular cartilage. We hypothesized that classical interstitial collagenases cleave collagen type II, leading to the increased expression of the 3/4 native type II collagen fragment (COL2-3/4C) and the corresponding denatured type II collagen fragment (COL2-3/4M), which could correlate with different cartilage destruction grades. In addition, we assessed whether these fragments could be measured in joint fluid and serve as diagnostic markers. METHODS: Cartilage specimens were obtained from the femoral heads of hip joints from total hip replacement operations. Articular gliding surfaces of the cartilage were categorized into normal (G0), fibrillated (G1), superficiallyfissured (G2) and deeplyfissured (fissures that reach to the subchondral bone) (G3). A histological scoring of the cartilage was also used. COL2-3/4C and COL2-3/4M were detected by immunohistochemical staining. Dot blotting was used to detect these fragments in joint fluid. RESULTS: COL2-3/4C and COL2-3/4M were found in the perichondrocyte matrix around lacunae. Such COL2-3/4C (p < 0.05) and COL2-3/4M (p < 0.05) immunoreactivity was significantly increased in G3 and G2 compared to GO and G1. A positive correlation (n = 35, Spearman rank correlation) was observed between the histological score and the percentage of COL2-3/4C positive lacunae (r = 0.43, p = 0.01) and COL2- 3/4M positive lacunae (r = 0.53, p = 0.001). All 7/7 joint fluid samples contained COL2-3/4C in dot blots whereas only 4/7 contained COL2-3/4M. CONCLUSION: Collagenase-cleaved collagen--both native and denatured--increases as the severity of OA increases, assessed using a macroscopic clinical and microscopic histological grading system. Collagen degradation was always most apparent around chondrocytes. Furthermore, the native COL2-3/4C fragment has potential as a joint fluid marker for OA.

Efferent targets of osseous CGRP-immunoreactive nerve fiber before and after bone destruction in adjuvant arthritic rat: an ultramorphological study on their terminal-target relations.

We report the ultramorphological characterization of the terminal-target relation of sensory peptidergic nerve fibers in healthy and diseased osseous tissues. Bone tissue sections were immunoelectronmicroscopically investigated for calcitonin gene-related peptide (CGRP), a neuropeptide widely distributed in sensory peptidergic fibers. Ultramorphological relation of the osseous CGRP-immunoreactive (ir) nerve terminals and their target cells was comparatively analyzed using healthy, arthritic, and postarthritic bone specimens from control and adjuvant-induced arthritic rats. Terminal-like profiles of the osseous CGRP-ir axons were evidenced in direct contact with the metaphyseal osteoblasts and osteoclasts of the control animals. Terminal-like profiles were also noted in the vicinity of the periosteal lining cells. Nonterminal-like profiles did not make intimate spatial relation to the cells/structures surrounding the nerve. Osseous CGRP-ir terminals and axons, which are either uncovered or thinly ensheathed by the supportive tissues, were extensively degenerated in adjuvant-induced infiltration, whereas larger fibers were relatively resistant. Numerous CGRP-ir axons with distinctive features reinnervated the postarthritic, ossifying periosteum. CGRP-ir axons appeared to reinnervate the eroded surface of metaphyseal bone and cartilage as early as the recruited osteoblasts resume osteogenesis in the postarthritic metaphysis. The observed terminal-target relations in the healthy and diseased bone tissues give an ultramorphological basis for the putative trophic, modulatory actions of CGRP innervation of the bone cells.

High-turnover periprosthetic bone remodeling and immature bone formation around loose cemented total hip joints.

Aseptic loosening and periprosthetic osteolysis are the major problems awaiting solution in total hip surgery. The clinical investigation focused on the analysis of periprosthetic bone remodeling to clarify one important key event in the cascade of periprosthetic connective tissue weakening and osteolysis around loose artificial hip joints. Twelve acetabular bone samples adjacent to granulomatous synovial-like membrane of loose hip prosthesis were retrieved at revision surgery and processed for Villanueva bone staining for morphological observation and bone histomorphometric analysis. Eight well-fixed bony samples were used as control. Although osteoclastic surface and eroded surface by osteoclasts were evident in the periprosthetic bone from loose hip joints (p = 0.003 and p = 0.027), increased osteoid/low-mineralized bone matrix (p < 0.001) and osteoid width (p < 0.001) also were significant findings in structural analysis. In addition, not only elevated mineral apposition rate (MAR; p = 0.044) but also increased mineralizing surface (p = 0.044) and bone formation rate (BFR; p = 0.002) in loose periprosthetic bones were shown in dynamic data analysis. These results were confirmed by precise morphological observation by confocal laser scanning microscopy. Active coupling of bone formation and resorption and increased osteocytes with abundant bone canalicular projections were found in combined with the presence of immature bone matrices (osteoid and low-mineralized bone areas) in periprosthetic bones from loose hip joints. These results indicated that active osteoclastic bone resorption and/or defective bone formation are coupled with monocyte/macrophage-mediated foreign body-type granuloma in the synovial-like interface membrane of loose hip joints. Thus, this unique high-turnover periprosthetic bone remodeling with bad bone quality probably is caused by the result of cellular host response combined with inappropriate cyclic mechanical loading. The fragile periprosthetic bone may contribute to hip prosthesis loosening.

Acid attack and cathepsin K in bone resorption around total hip replacement prosthesis.

Normal bone remodeling and pathological bone destruction have been considered to be osteoclast-driven. Osteoclasts are able to attach to bare bone surface and produce an acidic subcellular space. This leads to acid dissolution of hydroxyapatite, allowing cathepsin K to degrade the organic type I collagen-rich osteoid matrix under the acidic condition prevailing in Howship lacunae. Using a sting pH electrode, the interface membrane around a loosened total hip replacement prosthesis was found to be acidic. Confocal laser scanning disclosed irregular demineralization of the bone surface in contact with the acidic interface. Cathepsin K, an acidic collagenolytic enzyme, was found in interface tissue macrophages/giant cells and pseudosynovial fluid. Tissue extracts contained high levels of cathepsin K messenger RNA (mRNA) and protein. These observations suggest the presence of an acid- and cathepsin K-driven pathological mechanism of bone resorption, mediated not by osteoclasts in subosteoclastic space, but rather by the uncontrolled activity of macrophages in extracellular space.

Collagenase-3 (MMP-13) and its activators in rheumatoid arthritis: localization in the pannus-hard tissue junction and inhibition by alendronate.

The hypothesis of the present work was that the pannus tissue overlying the articular hard tissues has an aggressive phenotype and contains the newly discovered collagenase-3 and its endogenous inducers and activators. We therefore analyzed the eventual presence of collagenase-3 and its regulation at the pannus-cartilage junction. Collagenase-3 mRNA (in situ hybridization) and enzyme protein (ABC and immunofluorescence staining) were found in the pannocytes in the pannus-hard tissue junction. Inflammatory round cells associated with the critical interface contained TNF-alpha and IL-1beta. These cytokines induced collagenase-3 secretion in cultured rheumatoid synovial fibroblasts. Procollagenase-3 activators, stromelysin-1, 72 kDa type IV collagenase/gelatinase and membrane-type 1-MMP, were also found in the pannus-hard tissue junction. Active collagenase-3 was inhibited with alendronate (IC50 = 500-750 microM). Collagenase-3, due to its substrate profile and local synthesis in a milieu favoring its activation, might play a major role in the degradation of cartilage type II and bone type I collagens. Alendronate, at concentrations attainable in vivo, is able to inhibit collagenase-3. This might offer an option to control collagenase-3-mediated tissue destruction in rheumatoid arthritis.

New collagenolytic enzymes/cascade identified at the pannus-hard tissue junction in rheumatoid arthritis: destruction from above.

Our aim was to investigate the collagenolytic potential and localization of matrix metalloproteinase-2 (MMP-2) in relation to its regulatory proteins membrane type MT1-MMP and tissue inhibitor of metalloproteinases-2 (TIMP-2) in rheumatoid arthritis (RA). For this purpose, we have used purification of MMP-2, MMP-8, MMP-9 and interstitial type I, II and III collagens; SDS-PAGE/densitometric collagenase activity assay; zymography; Western blotting; reverse transcriptase polymerase chain reaction; in situ hybridization; and immunofluorescence, ABC, ABC-APAAP double immunostainings. MMP-2 degraded human type II collagen almost as effectively as MMP-8, whereas MMP-9 did not cleave type II collagen. In synovial tissue, MT1-MMP, TIMP-2 and MMP-2 were found in synovial lining in fibroblast- and macrophage-like cells, in stromal cells and in vascular endothelium. MT1-MMP, TIMP-2 and MMP-2 were strongly expressed in the pannocytes of the invasive pannus at the interface, but staining was weak and/or there were few positive cells both "above" and "below" the soft-to-hard tissue (cartilage and/or bone) interface. Rheumatoid synovial tissue extract contained proteolytically active 62/59 kDa MMP-2 and 43 kDa MT1-MMP, but no free TIMP-2. These results indicate that components of the ternary MT1-MMP/TIMP-2/MMP-2 complex are coexpressed in the normal synovial lining and in its pathological extension on the hyaline articular cartilage. MMP-2 may participate in the remodeling of the normal lining and also seems to be localized/focalized to pannocytes at a site critical for tissue destruction in arthritis.

Neural involvement in post-traumatic osteopenia: an experimental study in the rat.

The effect of sciatic nerve resection on post-traumatic bone loss and mechanical strength of the ipsilateral (IL) and contralateral (CL) femoral shafts and necks was studied 25 days after a tibial fracture. We subjected 45 male rats to a standardized tibial fracture, stabilized it with a modular intramedullary nail and then randomly allocated the animals to two groups: right sciatic nerve resection (SNR group) or sham operation (sham group). All of the operated hindlimbs were further immobilized in a plaster cast to avoid unequal loadbearing between the two groups. After 25 days of healing, 85Sr incorporation in the IL femora was 10% lower in the SNR group compared to the sham group, indicating a lower bone mineralization after sciatic nerve resection. The bone mineral content was 15% higher in the SNR group ipsilaterally. Accordingly, the bending moment and energy absorption in the femoral midshaft were higher in the SNR group compared to the sham group. The sciatic nerve resection protected the femoral shaft against the normally occurring post-traumatic bone loss after a tibial fracture. This protective effect of the neurectomy also occurred in the femoral neck, but not to the same extent. A protective effect was also present in the CL femur, suggesting additional systemic effects of the sciatic nerve resection.

Rapid proliferation of calcitonin gene-related peptide-immunoreactive nerves during healing of rat tibial fracture suggests neural involvement in bone growth and remodelling.

The nervous system may be actively involved in bone repair and in remodelling of callous tissue in bone fractures, as well as in the regulation of nociceptive impulses from the site of the trauma. The aim of this study was to assess the distribution and nature of the periosteal innervation of normal control bone and during bone healing subsequent to fracture of rat tibiae at seven, 14 and 21 days after experimental fracture using immunocytochemistry and image analysis quantification of the neuronal marker protein gene product 9.5 and sensory neuropeptide calcitonin gene-related peptide. At seven days, periosteal protein gene product 9.5- and calcitonin gene-related peptide-immunoreactive fibres showed dense ramifications and terminal sprouting. In addition to periosteum, the nerve fibres were found in the middle of the callus interspersed with inflammatory cells and penetrating into secondary minor fractures. At days 14 and 21 many tortuous nerves were found in the periosteum but not in mid callus. Image analysis quantification revealed a uniform increased proliferation of nerves after seven days. At 21 days, the intercept countings showed in excess of a three-fold increase of calcitonin gene-related peptide-immunoreactive nerve fibres compared with the normal control group (P > or = 0.0001) and were almost as numerous as protein gene product 9.5-immunoreactive fibres (P < 0.005). It is postulated that calcitonin gene-related peptide-containing sensory innervation may have a potential importance in the fracture vascular control, angiogenesis and osteogenesis in addition to a protective role against excessive fracture movement. The results are consistent with the neural involvement in bone growth and remodelling.

Collagenase in synovitis of rheumatoid arthritis.

There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.

Intravascular synovial sarcoma.

A biphasic synovial sarcoma occurring in the wall of a pathologically thickened femoral vein was diagnosed in a 34-year-old woman. This sarcoma was resected together with removal of a thrombus. A local recurrence was seen 5 years later, but the patient is alive and well 11 years after the first operation. Immunohistochemical evaluation revealed cytokeratin and epithelial membrane antigen in a portion of the tumor cells, as are typically seen in synovial sarcoma. This case shows that so-called synovial sarcoma may arise in places remote from any joints and that its origin may not be a synovial or perisynovial tissue in all cases. More likely, synovial sarcomas develop from transformed mesenchymal cells, some of which have acquired the epithelial phenotype.

Aortic ruptures in seat belt wearers.

Several investigations have indicated that rupture of the thoracic aorta is one of the leading causes of immediate death in victims of road traffic accidents. In Finland in 1983, 92% of front-seat passengers were seat belt wearers on highways and 82% in build-up areas. The mechanisms of rupture of the aorta have been intensively investigated, but the relationship between seat belt wearing and injury mechanisms leading to aortic rupture is still largely unknown. This study comprises 4169 fatally injured victims investigated by the Boards of Traffic Accident Investigation of Insurance Companies during the period 1972 to 1985. Chest injuries were recorded as the main cause of death in 1121 (26.9%) victims, 207 (5.0%) of those victims having worn a seat belt. Aortic ruptures were found at autopsy in 98 victims and the exact information of the location of the aortic tears was available in 68. For a control group, we analyzed 72 randomly chosen unbelted victims who had a fatal aortic rupture in similar accidents. The location of the aortic rupture in unbelted victims was more often in the ascending aorta, especially in drivers, whereas in seat belt wearers the distal descending aorta was statistically more often ruptured, especially in right-front passengers (p less than 0.05). The steering wheel predominated statistically as the part of the car estimated to have caused the injury in unbelted victims (37/72), and some interior part of the car was the most common cause of fatal thoracic impacts in seat belt wearers (48/68) (p less than 0.001). The mechanism of rupture of the aorta in the classic site just distal to the subclavian artery seems to be rapid deceleration, although complex body movements are also responsible in side impact collisions. The main mechanism leading to rupture of the ascending aorta seems to be severe blow to the bony thorax. This also often causes associated thoracic injuries, such as heart rupture and sternal fracture. Injuries in the ascending aorta were mostly found in unbelted victims and were sustained in frontal impact collisions, the injury-causing part of the car being the steering wheel. Ruptures of the distal descending part of the aorta were frequently associated with fractures of the thoracic vertebra.

Benign response to particles of diamond and SiC: bone chamber studies of new joint replacement coating materials in rabbits.

Wear particles from total joint replacements are thought to accelerate prosthetic loosening. Diamond coating may improve the smoothness and wear characteristics of the femoral head component of total hip replacements, and thus increase their longevity. The brittleness of a thin diamond coat may be overcome by using an SiC-whisker diamond composite. This study describes the reactions of regenerating bone tissue to phagocytosable particles of diamond and SiC, using implanted bone harvest chambers in rabbits. The particles were dispersed in hyaluronan and introduced into a canal transversing the implant. The tissue that entered the canal during the following 3 weeks was then harvested. In previous studies using this model, particles of high density polyethylene, bone cement and chromium-cobalt all caused an inflammatory reaction and a marked decrease in the amount of ingrown bone. In the present study, neither the diamond nor the SiC particles caused any decrease in bone formation. It appears that particles of diamond and SiC are comparatively harmless.

Human monocytes stimulation by particles of hydroxyapatite, silicon carbide and diamond: in vitro studies of new prosthesis coatings.

Aseptic loosening due to wear and debris formation constitutes the major problem in longevity of joint replacements. Diamond coated onto the prosthesis surface may reduce wear, owing to its excellent tribological properties. A thin diamond coating may be brittle, and we plan eventually to reinforce it with silicon carbide whiskers (SiC). In the present study we compared particles of diamond, SiC and hydroxyapatite (HA) in serum-free cultures of human monocytes. All particles were found to be phagocytozed, and monocyte morphology changed except after the ingestion of diamond. Interleukin-1 beta production was increased on average 30-fold and 38-fold in cultures exposed to HA and SiC, respectively, compared to control and diamond cultures (n = 6). Addition of the phagocytosis inhibitor cytochalasin B inhibited the morphological changes of the monocytes and reduced interleukin-1 beta production. In some experiments particles of polymethylmethacrylate were also included, and the interleukin-1 beta stimulation was in the same range as after HA and SiC stimulation. The results show that diamond particles in serum-free monocyte culture are inert, while SiC and HA have a stimulatory effect comparable to polymethylmethacrylate. With its excellent tribological and biocompatible properties, future studies with diamond coating are warranted.

Histological study of tissue reactions to epsilon-caprolactone-lactide copolymer in paste form.

In previous studies, epsilon-caprolactone-lactide copolymer in solid form has been used in experimental animals as suture material, and as a biodegradable nerve guide. The aim of the study reported here was to assess tissue reactions to epsilon-caprolactone-lactide copolymer in paste form, histologically, and to compare bone healing at the sites of implantation versus that at control sites. The other purpose of the study was to evaluate the properties of the implanted material as a filling material for bone defects. Resorption time and intensity of inflammatory reaction were also evaluated. Material was implanted into the abdominal walls and femurs of 34 rats. Follow-up times were from 2 weeks to 1 year. The results showed that epsilon-caprolactone-lactide copolymer in paste form induces a severe inflammatory reaction when placed in muscle, and moderate inflammation when implanted into bone. The resorption time was more than 1 year. Bone healing at sites of implantation was slower than at control sites.

Fibroblasts in synovitis in rheumatoid arthritis but not in noninflammatory synovial tissue in meniscus lesions express the carboxyterminal domain of procollagen type I.

Synovial tissue (ST) sections from patients with rheumatoid arthritis (RA) and meniscus lesions were stained using monoclonal antibodies against the carboxyterminal domain of human type I procollagen (alpha-pC) in avidin-biotin-peroxidase complex (ABC) staining. This gave a good signal-noise ratio and identified some synovial B-type lining cells and stromal fibroblasts in inflammatory RA ST but not in noninflammatory ST from patients with meniscus lesions. The authors' findings provide immunohistochemical evidence that the local fibroblasts in inflammatory ST in RA are activated, probably as a result of various humoral mediators produced in situ (by inflammatory mononuclear cells) in RA but not in normal noninflammatory ST.

Elastase activity, uninhibited by alpha 1-antitrypsin, in the periprosthetic connective matrix around loose total hip prostheses.

To clarify the proteolytic cascade in the loosening of total hip prostheses, the presence, tissue localization, and content of the serine proteinase, elastase, and its endogenous inhibitor, alpha 1-antitrypsin, were studied in periprosthetic tissues around 12 loose hip prostheses by immunohistochemistry, spectrophotometric enzyme assay, and immunoblot analysis, and the results were compared with those in control synovial tissue samples from eight knees. Increased numbers of elastase-immunoreactive cells and elevated elastase activity, inhibited by the addition of native alpha 1-antitrypsin, were observed both in the interface tissues between the bone and implants and in the pseudocapsular tissues from around loose hip prostheses. Elevated elastase activity, uninhibited by alpha 1-antitrypsin in situ and inhibited by the addition of native inhibitor, suggests a proteinase-inhibitor imbalance that contributes to the weakening of periprosthetic tissues and thus causes the loosening of hip prostheses.

Human neutrophil collagenase MMP-8 in peri-implant sulcus fluid and its inhibition by clodronate.

The exact molecular mechanisms of the loosening of a dental implant are not well-known. The characteristics of implant sulci are similar to those of periodontal sulci regarding gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF). Proteolytic enzymes, matrix metalloproteinases (MMPs), participate in peri-implant tissue remodeling. Clodronate is a well-tolerated bisphosphonate-group drug currently used in bone-resorption-related diseases in humans. The mechanisms of bisphosphonate action are not clarified. Collagenase activity in diseased PISF was significantly higher than in the clinically healthy group. Immunoblotting disclosed that diseased PISF contained increased immunoreactives MMP-8 compared with the healthy PISF. The residual latent collagenase activity in the diseased PISF was activated by gold thioglucose and inhibited completely by 100 microM of doxycycline closely resembling pure neutrophil collagenase (MMP-8). The presence of MMP-8 in diseased but not in clinically healthy PISF may prove to be a useful biochemical indicator to monitor peri-implant health and disease. Pure human neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth were efficiently inhibited in vitro by clodronate (50% inhibition [IC50] was achieved by 150 microM of clodronate), an osteoactive, antiresorptive bisphosphonate. Furthermore, the new finding suggests an extended and hitherto-undescribed potential for clodronate in preventing the loosening of both implants and teeth, based on a dual beneficial effect: prevention of both bone resorption/osteolysis and of soft tissue/dental ligament destruction. Potential new therapeutic indications based on the collagenase-inhibiting effect of clodronate provide potential new therapeutic indications for a variety of diseased involving connective tissue breakdown, such as periodontal disease, arthritides, and tumor invasion.

Expression of parathyroid hormone related protein in the tissue around loosened hip prostheses.

OBJECTIVE: To investigate the eventual presence and cellular source ofparathyroid hormone related protein (PTHrP) in the synovial-like interface membrane from aseptic loosening of total hip replacement (THR). METHODS: A polyclonal rabbit antiserum to the amino-terminal peptide of human PTHrP was used to stain 10 interface membrane samples from loose THR and 10 synovial tissue samples from hip osteoarthritis (OA). Quantitative microscopic assessment was done with a computer-assisted image analysis system. Western blotting was applied to verify the presence of PTHrP in both tissue samples. Double immunofluorescence labelling aimed to reveal the cellular sources of PTHrP. RESULTS: Immunoreactive PTHrP was found in all interface membrane and OA synovial tissue samples. The number of PTHrP positive cells in interface membrane was much higher than in OA synovial tissue. Positive cells were most commonly seen in the lining-like layers and sublining area of interface membrane. Double immunofluorescence labelling showed that most macrophages and fibroblasts in interface membrane were PTHrP positive. Western blotting revealed the 24-25 KD bands in both tissue samples. CONCLUSIONS: PTHrP expression is upregulated in interface membrane around loosened hip prostheses. Locally accumulated PTHrP may contribute to periprosthetic osteolysis and aseptic loosening of THR through its direct effects on bone, or indirectly via the induction of inflammatory mediators.

Ochronosis: a report of a case and a review of literature.

A patient with alkaptonuria and ochronotic pigment deposited in articular cartilage and sclerae clinically manifested a serious osteoarthritis of the peripheral and axial joints and synchondrosis, typically involved in long lasting cases of this hereditary defect of homogentisic acid oxidase. This is the first patient with this disorder reported, where a non-cemented total knee prosthesis (PCAR) was applied on both knees. This was possible due to the good quality of the bone stock, which did not seem to be impaired by ochronosis. Our patient had no cardiac symptoms or murmurs, but had a slight calcification in the annulus of aorta observed with echocardiography, a useful new method for screening this disease manifestation. A third new aspect reported is the immunopathology of the synovial tissue. Small pieces of torn-off cartilage were seen embedded in the synovial stroma. This was associated with a slight hyperplasia of the C3bi-receptor positive and proline hydroxylase positive type A and B synovial lining cells. Perivenular infiltrates contained CD2 positive T lymphocytes, mostly belonging to the CD4 subset, and some C3bi-receptor positive monocytes. Activated CD25 positive and immunoglobulin light chain positive T and B lymphocytes were absent or few. Because modern medicine has much to offer to those suffering from this ancient inborn error of metabolism in the form of new specific diagnostic methods and new surgical modes of treatment, such as endoprosthesis surgery and cardiac valve replacement, we also present a literature overview of this interesting condition.

Distribution of fibronectins and their integrin receptors in interface tissue from aseptic loosening of hip prostheses.

OBJECTIVES: To assess the distribution of fibronectins (FNs) and their integrin (Int) receptors in synovial membrane-like interface tissue (SMLIT) from aseptic loosening of total hip replacement (THR), and potential role of FN-Int interaction in the loosening process. METHODS: The alkaline phosphatase anti-alkaline phosphatase (APAAP) method was used to detect the distribution of FNs and their Int receptors in SMLIT and control samples. Double immunofluorescence labeling was used to reveal the different co-localizations. RESULTS: Intensive FN staining appeared in the lining layers, sublining area, and vascular endothelium, while immunoreactivities for Int alpha 4, alpha 5, beta 1 subunits were detected in the lining and endothelial cells of SMLIT. Immunofluorescence labeling revealed Int alpha 5 and collagenase-1/collagenase-3 double positive cells in lining layers and sublining area of SMLIT. CONCLUSION: Increased expression of FNs, Int alpha 4 beta 1 and alpha 5 beta 1 appeared in SMLIT compared with that in OA synovial membrane. FN-Int interactions may play a role in local collagenase production.