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Jordi Monfort

Publications and source records attributed to Jordi Monfort.

6 recordsLinked to original sources
PubMed2006

Degradation of small leucine-rich repeat proteoglycans by matrix metalloprotease-13: identification of a new biglycan cleavage site.

A major and early feature of cartilage degeneration is proteoglycan breakdown. Matrix metalloprotease (MMP)-13 plays an important role in cartilage degradation in osteoarthritis (OA). This MMP, in addition to initiating collagen fibre cleavage, acts on several proteoglycans. One of the proteoglycan families, termed small leucine-rich proteoglycans (SLRPs), was found to be involved in collagen fibril formation/interaction, with some members playing a role in the OA process. We investigated the ability of MMP-13 to cleave members of two classes of SLRPs: biglycan and decorin; and fibromodulin and lumican. SLRPs were isolated from human normal and OA cartilage using guanidinium chloride (4 mol/l) extraction. Digestion products were examined using Western blotting. The identities of the MMP-13 degradation products of biglycan and decorin (using specific substrates) were determined following electrophoresis and microsequencing. We found that the SLRPs studied were cleaved to differing extents by human MMP-13. Although only minimal cleavage of decorin and lumican was observed, cleavage of fibromodulin and biglycan was extensive, suggesting that both molecules are preferential substrates. In contrast to biglycan, decorin and lumican, which yielded a degradation pattern similar for both normal and OA cartilage, fibromodulin had a higher level of degradation with increased cartilage damage. Microsequencing revealed a novel major cleavage site (... G177/V178) for biglycan and a potential cleavage site for decorin upon exposure to MMP-13. We showed, for the first time, that MMP-13 can degrade members from two classes of the SLRP family, and identified the site at which biglycan is cleaved by MMP-13. MMP-13 induced SLRP degradation may represent an early critical event, which may in turn affect the collagen network by exposing the MMP-13 cleavage site in this macromolecule. Awareness of SLRP degradation products, especially those of biglycan and fibromodulin, may assist in early detection of OA cartilage degradation.

Adult↗
PubMed2006

Decreased metalloproteinase production as a response to mechanical pressure in human cartilage: a mechanism for homeostatic regulation.

Articular cartilage is optimised for bearing mechanical loads. Chondrocytes are the only cells present in mature cartilage and are responsible for the synthesis and integrity of the extracellular matrix. Appropriate joint loads stimulate chondrocytes to maintain healthy cartilage with a concrete protein composition according to loading demands. In contrast, inappropriate loads alter the composition of cartilage, leading to osteoarthritis (OA). Matrix metalloproteinases (MMPs) are involved in degradation of cartilage matrix components and have been implicated in OA, but their role in loading response is unclear. With this study, we aimed to elucidate the role of MMP-1 and MMP-3 in cartilage composition in response to mechanical load and to analyse the differences in aggrecan and type II collagen content in articular cartilage from maximum- and minimum-weight-bearing regions of human healthy and OA hips. In parallel, we analyse the apoptosis of chondrocytes in maximal and minimal load areas. Because human femoral heads are subjected to different loads at defined sites, both areas were obtained from the same hip and subsequently evaluated for differences in aggrecan, type II collagen, MMP-1, and MMP-3 content (enzyme-linked immunosorbent assay) and gene expression (real-time polymerase chain reaction) and for chondrocyte apoptosis (flow cytometry, bcl-2 Western blot, and mitochondrial membrane potential analysis). The results showed that the load reduced the MMP-1 and MMP-3 synthesis (p < 0.05) in healthy but not in OA cartilage. No significant differences between pressure areas were found for aggrecan and type II collagen gene expression levels. However, a trend toward significance, in the aggrecan/collagen II ratio, was found for healthy hips (p = 0.057) upon comparison of pressure areas (loaded areas > non-loaded areas). Moreover, compared with normal cartilage, OA cartilage showed a 10- to 20-fold lower ratio of aggrecan to type II collagen, suggesting that the balance between the major structural proteins is crucial to the integrity and function of the tissue. Alternatively, no differences in apoptosis levels between loading areas were found--evidence that mechanical load regulates cartilage matrix composition but does not affect chondrocyte viability. The results suggest that MMPs play a key role in regulating the balance of structural proteins of the articular cartilage matrix according to local mechanical demands.

Aged↗
PubMed2005

[Linguistic adaptation into Spanish and validation of the Arthritis Treatment Satisfaction Questionnaire].

BACKGROUND AND OBJECTIVE: Linguistic adaptation and validation into Spanish of the ARTS questionnaire, a self reported instrument designed to measure four osteoarthritis treatment satisfaction dimensions: treatment advantages, treatment convenience, apprehension about treatment and satisfaction with medical care. MATERIAL AND METHOD: Adaptation was performed using conceptual equivalence, supervised by a panel of 6 experts and 4 independent translators, who were in charge of performing translation and back-translation of the items. A sample of patients suffering from knee, hip or column osteoarthritis was used to estimate the psychometric properties of feasibility, reliability, validity and sensitivity to change. Three groups were identified: adequate analgesic effect and tolerability, treatment-switch because of a weak analgesic effect, and treatment- switch due to poor tolerability. The ARTS was administered at baseline, 1 week later for retest, and after 4 weeks of treatment with NSAIDs or Cox II-inhibitors. RESULTS: A sample of 163 patients was formed (67.7 [9.2] years old). No floor or ceiling effects were found, items were well understood and non- response rates were below 1%. Cronbach's alpha for the total scales was 0.85, and the intraclass correlation coefficient was 0.81. Exploratory factor analysis yielded 4 dimensions which were coherent with those proposed by the original authors. Concurrent validity was measured with SF-36, a pain VAS instrument, a treatment compliance VAS, and the Morisky-Green compliance questionnaire. The adapted instrument showed a good discriminatory validity, and it was able to distinguish between patients needing a change in treatment and those who did not need it. It was also sensitive to changes in patients' treatment effectiveness after a 30 days follow up. CONCLUSIONS: A psychometrically valid and conceptually equivalent ARTS questionnaire has been produced to explore satisfaction with treatment in patients with osteoarthritis in Spanish speaking countries.

Humans↗
PubMed2004

Sclerodermatomyositis associated with severe arthritis.

Overlap syndromes are a spectrum of diseases with clinical features of two or more classic connective tissue diseases. Polymyositis or dermatomyositis that is associated with features of systemic sclerosis, also called sclerodermatomyositis, is an uncommon overlap syndrome, with a rare antibody directed against the nucleolar antigen PM-Scl. This disease generally has good prognosis. We report a case of sclerodermatomyositis with an aggressive pulmonary and articular course.

Adult↗
PubMed2002

[Paget's disease of bone: study of 314 patients].

BACKGROUND: To describe the clinical and laboratory features of Paget's disease of bone at the time of diagnosis. PATIENTS AND METHOD: This multicenter and retrospective study included 314 patients. Diagnosis was performed by means of characteristic radiological findings and typical bone scintigraphy. The variables analyzed included: epidemiological variables, cause of diagnosis, bone involvement, disease extension (Coutris index), complications, alkaline phosphate (AP) levels and disease activity (Renier index). RESULTS: There were 159 (50.5%) males and the mean age was 64.9 years (SD 12.6). Diagnosis was casual in 228 (72.6%) patients. Polyostotic involvement was detected in 201 (63.9%) patients. More common locations were pelvis, skull and lumbar spine. Sacrum was more frequently involved in men than in women (p < 0.05), whereas skull involvement was more common in women (p < 0.05). The number of bones involved was 3.1 SD 3 and the percentage of skeletal involvement was 8.7 % (SD 6.5). One hundred ninety eigth (63%) patients had complications. The disease was active in 242 (77%) patients with a mean AP value of 377 IU/L (SD 493); the activity of the disease measured by the Renier index was 34 (SD 46); the activity was greater in the skull and the humerus. CONCLUSIONS: Paget's disease of bone is usually asymptomatic. Polyostotic involvement and activity are common at the time of diagnosis. Knowledge of the extension and activity by means of a mathematical model may aid to make therapeutical decisions.

Adult↗