Cartilage Oligometric Matrix Protein Research Articles

CHARACTERISTICS OF CYTOKINE REGULATION AND CARTILAGINOUS TISSUE METABOLISM AT PRIMARY AND POST-TRAUMATIC OSTEOARTHRITIS

Cytokine system and cartilaginous tissue metabolism of 27 women affected by 0-1 stage of primary and 19 women affected by 0-1 stage of post-traumatic osteoarthritis (OA) have been studied as well as of 10 healthy persons of the control group. The enzyme-linked immunoassay method was used to determine the content of cartilage oligometric matrix protein (СOMP), cartilage glucoprotein (YKL-40), interleukins (ILs) 4 and 1β in blood serum, collagen fragments (CTX II) in urine. It was found that СOMP, CTX II, YKL-40 and IL-1β concentrations grew at more intensive rate in case of primary OA compared to post-traumatic OA. The diminution of correlation relationship strength in IL-1β serum concentrations is noted with the system level of cartilaginous tissue degradation products on the background of YKL-40 regulatory influence buildup which is more prominent with primary OA than it is with the post-traumatic one. Conclusions: early stages of primary OA are characterized by more prominent degenerative changes in the joint hyaline cartilage due to losses of type II collagen and hyperproduction of proinflammatory link cytokines with the background of YKL-40 regulatory influence buildup and reduction of the IL-1β influence. The changes of cartilaginous tissue metabolism with post-traumatic OA were characterized by preservation of dependence on IL-1β serum concentration with the background of reduction of YKL-40 influence.

Effectiveness of Platelet-ich Plasma Based on Gene Expression in Knee Osteoarthritis.

Intra-articular injection of Platelet-rich plasma (PRP) is an effective method for the treatment of patients with knee osteoarthritis (OA). This study aimed to assess the effects of PRP injection on OA, based on gene expression analysis. A sample of 30 subjects with knee OA was asked to complete the Persian versions of the Intermittent and Constant Osteoarthritis Pain (ICOAP) and Knee and Osteoarthritis Outcome Score (KOOS). Thereafter, the expression of IGF-1, HIF-1, cartilage oligometric matrix protein (COMP), and bone morphogenetic proteins (BMP2) were compared in the patient before and 1 month after PRP injection using real-time polymerase chain reaction (PCR). According to the results of the study, the expression of IGF-1, HIF-1, COMP and BMP2 were reported to be higher in subjects with PRP injection; however, only the up-regulation of IGF-1 was statistically significant (P<007). Moreover, the significant change in the KOOS and ICOAP scores was attributed to PRP injection (P<0.01). Intra-articular injections of PRP were reported to ease the pain, decrease the stiffness, and improve quality of life in patients with knee OA through the promotion of IGF-1 expression.

Combination of novel and tradition biomarkers to enhance diagnostic sensitivity and specificity for early diagnosis of rheumatoid arthritis and seronegative rheumatoid arthritis

Background and objective: Rheumatoid arthritis is an autoimmune disease. This study investigated the potential value of combining cartilage oligometric matrix protein, anti-cyclic citrullinated protein, and 14-3-3 eta protein with traditional biomarkers to reduce the diagnostic gap. Methods: This case-control study included 46 male and female patients and 42 age- and gender-matched adults as control group. The biomarkers were measured using ELISA technique. Results: Tests for anti-cyclic citrullinated protein and cartilage oligometric matrix protein are excellent tools to diagnose rheumatoid arthritis because anti-cyclic citrullinated protein and cartilage oligometric matrix protein are associated with the highest ROC area. The validity of the test for 14-3-3 eta protein, which is a good test to predict rheumatoid arthritis, ranks second. The optimum cut-off values for high cartilage oligometric matrix protein, high anti-cyclic citrullinated protein, and high 14-3-3 eta protein were ≥0.242µg/L, ≥0.566ng/L, and ≥0.145ng/L, respectively. 14-3-3η protein, cartilage oligometric matrix protein status as a parallel combination which is considered as a wonderful combination in classification criteria for rheumatoid arthritis. Parallel combination, both criteria two tests are positive, namely “high cartilage oligometric matrix protein (≥0.242) + high 14-3-3η protein (≥0.145)” was associated with a perfect test, that the patients have rheumatoid arthritis (sensitivity 100%, specificity 100%, accuracy 100%, positive predictive value at pre-test probability 50% and 90% = 100%). A positive test using this combination is 100% diagnostic and establishes a possible diagnosis of rheumatoid arthritis with 100%, while a negative test would exclude a possible diagnosis of rheumatoid arthritis with 100% confidence. Conclusion: Results confirmed that high serum level of cartilage oligometric matrix protein, anti-cyclic citrullinated protein, and 14-3-3 eta protein are significantly associated with increased risk for rheumatoid arthritis, demonstrating the potential value of combining these new biomarkers with traditional biomarkers to enhance diagnostic sensitivity and specificity and ultimately reduce the diagnostic gap.

Gene expression profiling of chondrogenic differentiation by dexamethasone-conjugated polyethyleneimine with SOX trio genes in stem cells

BackgroundDuring differentiation of stem cells, it is recognized that molecular mechanisms of transcription factors manage stem cells towards the intended lineage. In this study, using microarray-based technology, gene expression profiling was examined during the process of chondrogenic differentiation of human mesenchymal stem cells (hMSCs). To induce chondrogenic differentiation of hMSCs, the cationic polymer polyethyleneimine (PEI) was coupled with the synthetic glucocorticoid dexamethasone (DEX). DEX/PEI could be polyplexed with anionic plasmid DNAs (pDNAs) harboring the chondrogenesis-inducing factors SOX5, SOX6, and SOX9. These are named differentiation-inducing nanoparticles (DI-NPs).MethodsA DI-NP system for inducing chondrogenic differentiation was designed and characterized by dynamic light scattering and scanning electron microscopy (SEM). Chondrogenic induction of hMSCs was evaluated using various tools such as reverse-transcription polymerase chain reaction (RT-PCR), Western blotting, confocal fluorescent microscopy, and immunohistochemistry analysis. The gene expression profiling of DI-NP-treated hMSCs was performed by microarray analysis.ResultsThe hMSCs were more efficiently transfected with pDNAs using DI-NPs than using PEI. Moreover, microarray analysis demonstrated the gene expression profiling of hMSCs transfected with DI-NPs. Chondrogenic factors including SOX9, collagen type II (COLII), Aggrecan, and cartilage oligometric matrix protein (COMP) were upregulated while osteogenic factors including collagen type I (COLI) was downregulated. Chondrogenesis-induced hMSCs were better differentiated as assessed by RT-PCR, Western blotting analyses, and immunohistochemistry.ConclusionDI-NPs are good gene delivery carriers and induce chondrogenic differentiation of hMSCs. Additionally, comprehensive examination of the gene expression was attempted to identify specific genes related to differentiation by microarray analysis.Graphical abstract

Spinacia oleracea extract attenuates disease progression and sub-chondral bone changes in monosodium iodoacetate-induced osteoarthritis in rats

BackgroundSpinacia oleracea is an important dietary vegetable in India and throughout the world and has many beneficial effects. It is cultivated globally. However, its effect on osteoarthritis that mainly targets the cartilage cells remains unknown. In this study we aimed to evaluate the anti-osteoarthritic and chondro-protective effects of SOE on chemically induced osteoarthritis (OA).MethodsOA was induced by intra-patellar injection of monosodium iodoacetate (MIA) at the knee joint in rats. SOE was then given orally at 250 and 500 mg.kg− 1 day− 1 doses for 28 days to these rats. Anti-osteoarthritic potential of SOE was evaluated by micro-CT, mRNA and protein expression of pro-inflammatory and chondrogenic genes, clinically relevant biomarker’s and behavioural experiments.ResultsIn vitro cell free and cell based assays indicated that SOE acts as a strong anti-oxidant and an anti-inflammatory agent. Histological analysis of knee joints at the end of the experiment by safranin-o and toluidine blue staining established its protective effect. Radiological data corroborated the findings with improvement in the joint space and irregularity of the articular and atrophied femoral condyles and tibial plateau. Micro-CT analysis of sub-chondral bone indicated that SOE had the ability to mitigate OA effects by increasing bone volume to tissue volume (BV/TV) which resulted in decrease of trabecular pattern factor (Tb.Pf) by more than 200%. SOE stimulated chondrogenic marker gene expression with reduction in pro-inflammatory markers. Purified compounds isolated from SOE exhibited increased Sox-9 and Col-II protein expression in articular chondrocytes. Serum and urine analysis indicated that SOE had the potential to down-regulate glutathione S-transferase (GST) activity, clinical markers of osteoarthritis like cartilage oligometric matrix protein (COMP) and CTX-II. Overall, this led to a significant improvement in locomotion and balancing activity in rats as assessed by Open-field and Rota rod test.ConclusionOn the basis of in vitro and in vivo experiments performed with Spinacea oleracea extract we can deduce that SOE has the ability to alleviate the MIA induced deleterious effects.

Correction: Correlation of serum cartilage oligometric matrix protein (COMP) and interleukin-16 (IL-16) levels with disease severity in primary knee osteoarthritis: A pilot study in a Malaysian population.

[This corrects the article DOI: 10.1371/journal.pone.0184802.].

Correlation of serum cartilage oligomeric matrix protein (COMP) and interleukin-16 (IL-16) levels with disease severity in primary knee osteoarthritis: A pilot study in a Malaysian population.

ObjectiveThe aim of this study was to investigate the correlations between serum cartilage oligomeric matrix protein (COMP), interleukin-16 (IL-16) and different grades of knee osteoarthritis (KOA) in Malaysian subjects.MethodsNinety subjects were recruited comprising 30 with Kellgren-Lawrence (K-L) grade 2 KOA, 27 with K-L grade 3 KOA, 7 with grade 4 KOA, and 30 healthy controls. All subjects completed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire. Serum COMP and IL-16 levels were measured using ELISA and their values log transformed to ensure a normal distribution.ResultsThere was no significant differences in levels of log serum COMP and IL-16 between healthy controls and KOA patients. There were no significant differences in the log serum COMP and IL-16 levels within the different K-L grades in the KOA patients. In KOA patients, log serum IL-16 levels significantly correlated with the WOMAC score (p = 0.001) and its subscales, pain (p = 0.005), stiffness (p = 0.019) and physical function (p<0.0001). Serum IL-16 levels were significantly higher in Malaysian Indians compared to Malays and Chinese (p = 0.024).ConclusionsIn this multi-ethnic Malaysian population, there was no difference in serum COMP and IL-16 levels between healthy controls and patients with KOA, nor was there any difference in serum COMP or IL-16 levels across the various K-L grades of KOA. However, there were significant inter-racial differences in serum IL-16 levels.

Anti-ulcerative, Anti-oxidative, and Anti-inflammatory Effects of Rosuvastatin and Isosorbide Dinitrate on Cysteamine-Induced Chronic Duodenal Ulcer in Rats

Background: Methotrexate (MXT) is the corner stone in treatment of rheumatoid arthritis. Although methotrexate is usually administrated in low weakly dose in patients with rheumatoid arthritis discontinuation rates are as high as 16% due to adverse effects. Hepatotoxicity is the most common side effect after long term course of methotrexate. Aim of the study: This work aimed to investigate the potential effect of sitagliptin alone and in combination with different doses of methotrexate on rheumatoid arthritis (RA) induced experimentally in rats. Moreover, we investigated the benefits of sitaglipitn co-administration with methotrexate not only on RA progression, but also on organs commonly injured on using methotrexate alone as a disease-modifying anti-rheumatic drug such as the liver. Methods: 42 male adult Sprague Dawley rats divided into seven equal groups: Normal control group, None treated Freund,s adjuvant induced rheumatoid arthritis,High dose MXT treated rheumatoid arthritis (1 mg/kg/3 days i.p.) over 4 weeks,Sitagliptin treated rheumatoid arthritis (10 mg/kg/day p.o) for 4 weeks, high dose MXT+ sitagliptin treated arthritis, 1/2 dose MXT+ sitagliptin treated arthritis, 1/4 dose MXT+ sitagliptin treated arthritis. Serological parameters namely, cyclic citrullinated peptide antibodies (Anti-CCP), matrix metalloproteinase-3(MMP-3), cartilage oligometric matrix protein (COMP) and TNF-α level were measured. Liver tissue and hind paw joint were subjected to histopathological examination. Results: Best degree of improvement was obtained with high dose MXT+ sitagliptin. It is significantly better than that of either drug alone. Half dose of MXT /sitagliptin combination was proved to be equally effective to the full dose of methotrexate alone regarding all tested parameters. Conclusion: concomitant administration of sitagliptin augmented immunosuppressive effect and ameliorated hepatotoxicity of methotrexate in Freund,s adjuvant model of rheumatoid arthritis.

English

Vibration is a mechanical stimulus that is characterized by an oscillatory motion. When there is a direct contact of a person, in general standing on the base of this type of platform, the vibration that is produced in these machines is transmitted to the body of the subject producing whole body vibration (WBV) exercises. Biological effects can be associated with the WBV exercises with desirable and undesirable consequences. These effects of the WBV exercises seem to be related to a direct effect in a tissue/organ/system and/or or to indirect effects due to alteration of the plasma concentration of some hormonal and non hormonal biomarkers. The aim of this investigation is to present a revision about hormonal and non hormonal biomarkers in human beings submitted to WBV exercises that have suffered alteration in the plasma concentrations. Searches were performed in the PubMed and Scopus databases with the key words &ldquo;whole body vibration&rdquo;. Papers were selected following defined criteria. Considering the WBV exercise, hormonal fluctuations of testosterone, growth, insulin-like growth factor1, epinephrine, norepinephrine, cortisol, irisin, parathyroid hormone and sclerotin are observed. Non hormonal biomarkers have suffered alterations in response to WBV, as glucose, free fatty acids, adiponectin, transforming growth factor-beta1, nitric oxide, osteopontin, interleukin-1beta, bone-specific alkaline phosphatase, cartilage oligometric matrix protein and tumor necrosis factor-alpha in plasma concentration. In conclusion, putting together the findings related to the alterations of the concentration of hormonal and non hormonal biomarkers due to the WBV exercises, it is possible that the fluctuations in the plasma concentrations of these biomarkers might help us understand better the biological effects of this kind of exercises, probably due to neuroendrocrine responses. &nbsp; Key words: Whole body vibration exercise, vibration, hormonal and non hormonal fluctuations &nbsp

Serum Cartilage Oligometric Matrix Protein and Pettersson Scoring System As an Index for Hemophilic Arthropathy

▪The pathogenesis of hemophilic arthropathy is multifactorial, with changes occurring in the synovium, bone, cartilage, and blood vessels. Recurrent joint bleeding causes synovial proliferation and inflammation (hemophilic synovitis) that contributes to end stage degeneration (hemophilic arthropathy); with pain and limitation of motion that severely affects patients’ quality of life.The aim of the present study was to evaluate the degree of joint damage in boys with hemophilia using plain x-ray, and to measure serum level of human cartilage oligomeric matrix protein, to determine its relation to the degree of joint damage.The study was carried out on thirty boys with hemophilic arthropathy (group I) and ten healthy boys were included as control (group II).All hemophilic patients were scored for Functional independence score (FISH score) in hemophilia and radiological changes (Pettersson’s score) using conventional frontal and lateral radiographs of the most affected joint.Factor activity level was measured for all hemophilic patients while serum cartilage oligomeric matrix protein (COMP) was measured for hemophilic patients and control group.Among the thirty hemophilic patients, 26 (86.7%) patients were hemophilia A and 4 (13.3%) patients were hemophilia BAll patients were receiving on demand replacement therapy using plasma derived Factor concentrate or fresh frozen plasma (FFP) according to availability.Fifteen patients (50%) had severe hemophilia, 7 (23.3%) had moderate and 8(26.72%) had mild hemophilia.A higher serum level of COMP with a mean of 757± 211.30 in the severe hemophiliacs, and a mean of 403.57 ± 86.49 and 211.25 ± 74.26 in the moderate and mild hemophiliacs respectively the difference was statistically significant (p < 0.001).Serum level of COMP in group I was significantly higher than in group II (p=0.004) with significant negative correlation with FISH score (r=-0.435 p=0.016). COMP correlated positively with joint space narrowing of the Pettersson score (r=0.421 p<0.001) and with total Pettersson score (r=0.421 p=0.020).The number of joints affected (during life) of hemophilic patients ranged between 1-12 with a mean of 5.50 ± 2.46 Joints. A significant positive correlation between serum level of COMP and number of joints affected (r = 0.487, p = 0.006).Joint space narrowing is the most important indicator of cartilage loss. Serum COMP level is indicative of the amount of joint damage in patients with hemophilic arthropathy.The combined scoring of functional independence and Pettersson in addition with serum levels of COMP give a good overview of the degree of hemophilic arthropathy DisclosuresNo relevant conflicts of interest to declare.

AB0825 Investigation of Effects on Bone Metabolism of Anti-TNF BIOLOGICS and Bisphosphonates in Patients with Rheumatoid Arthritis

BackgroundTreatment for rheumatoid arthritis has become to obtain remission as biologics are widely used. Nonetheless, the main target of the treatment is synovitis and evaluation and treatment for osteoporosis with...

Clinical Significance of Cartilage Biomarkers for Monitoring Structural Joint Damage in Rheumatoid Arthritis Patients Treated with Anti-TNF Therapy

PurposeWith the current use of biologics in rheumatoid arthritis (RA), there is a need to monitor ongoing structural joint damage due to the dissociation of articular cartilage damage from disease activity of RA. This study longitudinally analyzed levels of serum cartilage biomarkers during 54 weeks of infliximab therapy, to evaluate the feasibility of biomarkers for monitoring structural joint damage.MethodsSubjects comprised 33 patients with early RA and 33 patients with established RA. All patients received 3 mg/kg of infliximab and methotrexate for 54 weeks. Levels of the following serum cartilage markers were measured at baseline and at weeks 14, 22, and 54: hyaluronan (HA); cartilage oligometric matrix protein (COMP); type II collagen (CII)-related neoepitope (C2C); type II procollagen carboxy-propeptide (CPII); and keratin sulfate (KS). Time courses for each biomarker were assessed, and relationships between these biomarkers and clinical or radiographic parameters generally used for RA were investigated.ResultsLevels of CRP, MMP-3, DAS28-CRP, and annual progression of TSS were improved to similar degrees in both groups at week 54. HA and C2C/CPII were significantly decreased compared to baseline in the early RA group (p<0.001), whereas HA and COMP, but not C2C/CPII, were decreased in the established RA group. Strikingly, serum C2C/CPII levels were universally improved in early RA, regardless of EULAR response grade. Both ΔHA and ΔC2C/CPII from baseline to week 54 correlated significantly with not only ΔCRP, but also ΔDAS28 in early RA. Interestingly, when partial correlation coefficients were calculated by standardizing CRP levels, the significant correlation of ΔHA to ΔDAS28 disappeared, whereas correlations of ΔC2C/CPII to ΔDAS28, ΔJNS, and ΔHAQ remained significant. These results suggest a role of ΔC2C/CPII as a marker of ongoing structural joint damage with the least association with CRP, and that irreversible cartilage damage in established RA limits restoration of the C2C/CPII level, even with tight control of joint inflammation.ConclusionThe temporal course of C2C/CPII level during anti-TNF therapy indicates that CII turnover shifts toward CII synthesis in early RA, but not in established RA, potentially due to irreversible cartilage damage. ΔC2C/CPII appears to offer a useful marker reflecting ongoing structural joint damage, dissociated from inflammatory indices such as CRP and MMP-3.

Increased serum cartilage oligometric matrix protein (COMP) levels in knee osteoarthritis

Increased serum cartilage oligometric matrix protein (COMP) levels in knee osteoarthritis

Vibration training intervention to maintain cartilage thickness and serum concentrations of cartilage oligometric matrix protein (COMP) during immobilization

To test the hypotheses that 1) 14-days of immobilization of young healthy subjects using a 6 degrees -"head-down-tilt-bed-rest"-model (6 degrees -HDT) would reduce cartilage thickness in the knee and serum Cartilage oligometric matrix protein (COMP) concentration and 2) isolated whole body vibration training would counteract the bed rest effects. The study was performed and designed in compliance with the Declaration of Helsinki and is registered as trial DRKS00000140 in the German Clinical Trial Register (register.germanctr.de). Eight male healthy subjects (78.0+/-9.5kg; 179+/-0.96cm, 26+/-5 years) performed 14 days of 6 degrees -HDT. The study was designed as a cross-over-design with two study phases: a training and a control intervention. During the training intervention, subjects underwent 2x5-min whole body vibration training/day (Frequency: 20Hz; amplitude: 2-4mm). Magnetic resonance (MR) images (slice thickness: 2mm; in-plane resolution: 0.35x0.35mm; pixels: 448x512) were taken before and after the 6 degrees -HDT periods. Average cartilage thicknesses were calculated for the load bearing regions on the medial and lateral articulating surfaces in the femur and tibia. While the control intervention resulted in an overall loss in average cartilage thickness of -8% (pre: 3.08mm+/-0.6mm post: 2.82mm+/-0.6mm) in the weight-bearing regions of the tibia, average cartilage thickness increased by 21.9% (pre: 2.66mm+/-0.45mm post: 3.24mm+/-0.63mm) with the vibration intervention. No significant differences were found in the weight-bearing regions of the femur. During both interventions, reduced serum COMP concentrations were observed (control intervention: -13.6+/-8.4%; vibration intervention: -9.9+/-3.3%). The results of this study suggest that articular cartilage thickness is sensitive to unloading and that vibration training may be a potent countermeasure against these effects. The sensitivity of cartilage to physical training is of high relevance for training methods in space flight, elite and sport and rehabilitation after illness or injury.

Cartilage Oligometric Matrix Protein-Angiopoietin-1 Promotes Revascularization Through Increased Survivin Expression in Dermal Endothelial Cells of Skin Grafts in Mice

The present study examined the effects of cartilage oligometric matrix protein angiopoietin-1 (COMP-Ang1) on the revascularization of mice skin grafts. Full-thickness skin grafts were autotransferred into BALB/c mice. The donor grafts were soaked in COMP-Ang1 protein (50 mug/ml, n = 10) or in bovine serum albumin (BSA) (50 mug/ml, n = 10) dissolved in 1 ml of sterile, phosphate-buffered saline for 5 minutes before transfer. Revascularization of the grafts was monitored using an intravital microscope on postoperative days 3, 4, and 5. Morphological and immunohistochemical analyses were performed to evaluate platelet-endothelial cell adhesion molecule-1 and survivin expression and apoptotic signal in the transplanted grafts. Grafts soaked in COMP-Ang1 (COMP-Ang1 group) showed significantly increased revascularization compared with grafts soaked in BSA (BSA group) on intravital microscopy and platelet-endothelial cell adhesion molecule-1 staining. The COMP-Ang1 group showed a significant increase of survivin expression in the endothelial cells and a reduction of apoptotic signal in comparison to the BSA group. Therefore, we believe that COMP-Ang1 provides the therapeutic benefit of enhancing the survival of vascular endothelial cells during transplantation of skin graft.

P96 EFFECT OF OVER-THE-COUNTER DOSES OF NAPROXEN SODIUM ON INHIBITION OF PLATELET CYCLOOXYGENASE-1 IN HEALTHY VOLUNTEERS

of lead on putative OA biomarkers. We examined whole blood Pb levels and OA biomarkers in African American and white women. Methods: A total of 339 women in the Johnston County OA Project Metals Exposure Sub-study (mean age 62.5 (9.4) years, 35% African American) had available whole blood, serum, or urine samples for whole blood lead and biomarkers assessments. Whole blood lead was measured by inductively coupled plasma mass spectrometry at the Inorganic Toxicology laboratory, Division of Laboratory Sciences, National Center for Environmental Health, CDC, Atlanta, Georgia. Urine C-telopeptide fragments of type II collagen (CTX-II), cross linked N telopeptide of type I collagen (NTX-I), serum hyaluronic acid (HA) and cartilage oligometric matrix protein (COMP) were measured by commercially available kits. Radiographic knee OA (rKOA) was defined by Kellgren-Lawrence grades (2-4) with fixed-flexion posterioranterior knee films. Pearson correlation coefficients were calculated between Log Pb and log of each biomarker. Analysis of covariance models were used to examine associations between blood lead levels and the 4 chosen biomarkers with log transformed biomarkers as outcomes, adjusted for age, race, BMI, and rKOA variables. Effect modification between log Pb and race were examined, with significance defined by p-values 0.20). In adjusted models, log Pb was associated with mean log CTX-II (p = 0.007), NTX-I (p <0.001), and COMP (p = 0.036), but not with mean log HA (p = 0.9). There were no notable race and log Pb interactions. Conclusions: Mean blood Pb levels are associated with urine CTX-II, urine NTX-I, and serum COMP, but not serum HA in both African American and white women. These data suggest that Pb has an effect not only on bone collagen, but also on type II collagen and non-collagenous matrix proteins. Potential effects of Pb in the pathogenesis of OA, then, are likely to be related to alterations in these factors, but not to effects on synovial inflammation. We are planning further studies to delineate how Pb may affect joint structures and how other factors such as menopause, hormone replacement therapy, and bone density, might influence these associations.

Is the upregulation of bradykinin B2 receptors by TGF-β1 one of the missing pieces in the “airway hyperresponsiveness” puzzle?

transforming growth factor (TGF)-β1 belongs to the TGF-β family of proteins corresponding to a set of pleiotropic secreted signaling molecules with unique and potent immunoregulatory properties ([10][1]). TGF-β1 is produced by every leukocyte lineage, including lymphocytes, macrophages, and