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Biomedical subjects

Martin Lavigne

Publications and source records attributed to Martin Lavigne.

7 recordsLinked to original sources
PubMed2006

Identification in human osteoarthritic chondrocytes of proteins binding to the novel regulatory site AGRE in the human matrix metalloprotease 13 proximal promoter.

OBJECTIVE: Matrix metalloprotease 13 (MMP-13) plays a major role in osteoarthritic (OA) processes. We previously identified the AG-rich element (AGRE) regulatory site (GAAAAGAAAAAG) in the proximal promoter of this gene. Electrophoretic mobility shift assays (EMSAs) done with nuclear extracts from OA chondrocytes showed the presence of 2 AGRE protein-binding complexes, the formation of which depended on the pathophysiologic state (high or low) of the cells; the low OA (L-OA) chondrocytes have low MMP-13 basal levels and high interleukin-1beta (IL-1beta) inducibility, and the high OA (H-OA) chondrocytes have high MMP-13 basal levels and low IL-1beta inducibility. In this study, we sought to determine the importance of individual AGRE bases in promoter activity and to identify AGRE binding proteins from L-OA and H-OA chondrocyte complexes. METHODS: Promoter activity was determined following transient transfection into human OA chondrocytes. AGRE binding proteins were identified by mass spectroscopy. RESULTS: Individual mutations of the AGRE site differentially modulated promoter activity, indicating that the intact AGRE site is required for optimal MMP-13 expression. Damage-specific DNA binding protein 1 (DDB-1) was identified in the L-OA chondrocyte-binding complex. EMSA experiments performed with the mutation of the left AGRE site (GTGCTGAAAAAG) and nuclear extracts of L-OA chondrocytes reproduced the pattern seen in the H-OA chondrocytes. Mass spectroscopy identified p130cas as one of the proteins in this complex. Supershift experiments showed the presence of p130cas and nuclear matrix transcription factor 4 (NMP-4) in the wild-type AGRE/H-OA chondrocyte complex. CONCLUSION: These data suggest that the binding of p130(cas) and NMP-4 to the AGRE site regulates MMP-13 expression and may trigger the change in human chondrocytes from the L-OA state to the H-OA state.

Base Sequence↗
PubMed2006

A multimodal analgesia protocol for total knee arthroplasty. A randomized, controlled study.

BACKGROUND: Although numerous methods of postoperative analgesia have been investigated in an attempt to improve pain control after total knee arthroplasty, parenteral narcotics still play a major role in postoperative pain management. Local anesthetics have the advantage of blocking pain conduction at its origin and minimizing the systemic side effects associated with postoperative narcotic use. This study was performed to evaluate the benefits and safety of a multimodal analgesia protocol that included periarticular injection of large doses of local anesthetics in patients undergoing total knee arthroplasty. METHODS: We compared morphine consumption during the first twenty-four hours after unilateral total knee arthroplasty in forty-two patients who had been randomized to receive either (1) a perioperative infiltration mixture, consisting principally of local anesthetic, and self-administered morphine or (2) self-administered morphine only. Narcotics consumption, pain control, medication-related side effects, plasma levels of the local anesthetic (ropivacaine), and postoperative rehabilitation were monitored. RESULTS: Although there was high satisfaction and good pain control in both groups, morphine consumption was significantly lower in the local analgesia group than it was in the control group (28.8 +/- 17.4 mg compared with 50.3 +/- 25.4 mg twenty-four hours after surgery, and 46.7 +/- 19.4 mg compared with 68.6 +/- 38.6 mg forty hours after surgery). Both groups achieved a similar amount of knee flexion on the fifth postoperative day. Over the five-day period after the procedure, the patients in the local analgesia group reported a total of 2.6 +/- 3.9 hours of nausea compared with 7.1 +/- 12.2 hours in the control group. No complications related to the infiltration of the local anesthetic were observed, and all plasma concentrations of the local anesthetic were below the toxic range. CONCLUSIONS: This multimodal perioperative analgesia protocol that included infiltration of a local anesthetic offered improved pain control and minimal side effects to patients undergoing total knee arthroplasty. Our study also confirmed the safety of the protocol.

Analgesia, Patient-Controlled↗
PubMed2005

Distribution of vascular foramina around the femoral head and neck junction: relevance for conservative intracapsular procedures of the hip.

Precise knowledge of femoral head vascular anatomy is mandatory for the safe execution of intracapsular surgical procedures aimed at preserving the hip joint. No quantitative topographic data exist concerning the exact location and distribution of the entrance of these vessels through nutrient vascular foramina at the femoral head and neck junction. This study shows that only a few significant retinacular vessels may reach the adult femoral head on its anterior aspect and that most vascular foramina are located close to the antero- and posterosuperior regions of the femoral head and neck junction. This larger segment should be carefully protected during any conservative intracapsular procedure of the hip and may be desirable in femoral head resurfacing arthroplasty.

Arthroplasty, Replacement, Hip↗
PubMed2004

Activation of peroxisome proliferator-activated receptor gamma inhibits interleukin-1beta-induced membrane-associated prostaglandin E2 synthase-1 expression in human synovial fibroblasts by interfering with Egr-1.

Membrane-associated prostaglandin (PG) E(2) synthase-1 (mPGES-1) catalyzes the conversion of PGH(2) to PGE(2), which contributes to many biological processes. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor and plays an important role in growth, differentiation, and inflammation in different tissues. Here, we examined the effect of PPARgamma ligands on interleukin-1beta (IL-1beta)-induced mPGES-1 expression in human synovial fibroblasts. PPARgamma ligands 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)) and the thiazolidinedione troglitazone (TRO), but not PPARalpha ligand Wy14643, dose-dependently suppressed IL-1beta-induced PGE(2) production, as well as mPGES-1 protein and mRNA expression. 15d-PGJ(2) and TRO suppressed IL-1beta-induced activation of the mPGES-1 promoter. Overexpression of wild-type PPARgamma further enhanced, whereas overexpression of a dominant negative PPARgamma alleviated, the suppressive effect of both PPARgamma ligands. Furthermore, pretreatment with an antagonist of PPARgamma, GW9662, relieves the suppressive effect of PPARgamma ligands on mPGES-1 protein expression, suggesting that the inhibition of mPGES-1 expression is mediated by PPARgamma. We demonstrated that PPARgamma ligands suppressed Egr-1-mediated induction of the activities of the mPGES-1 promoter and of a synthetic reporter construct containing three tandem repeats of an Egr-1 binding site. The suppressive effect of PPARgamma ligands was enhanced in the presence of a PPARgamma expression plasmid. Electrophoretic mobility shift and supershift assays for Egr-1 binding sites in the mPGES-1 promoter showed that both 15d-PGJ(2) and TRO suppressed IL-1beta-induced DNA-binding activity of Egr-1. These data define mPGES-1 and Egr-1 as novel targets of PPARgamma and suggest that inhibition of mPGES-1 gene transcription may be one of the mechanisms by which PPARgamma regulates inflammatory responses.

Amino Acid Motifs↗
PubMed2004

Regulation of the expression of 5-lipoxygenase-activating protein/5-lipoxygenase and the synthesis of leukotriene B(4) in osteoarthritic chondrocytes: role of transforming growth factor beta and eicosanoids.

OBJECTIVE: To explore the modulation of 5-lipoxygenase-activating protein (FLAP) and 5-lipoxygenase (5-LOX) expression in human osteoarthritic (OA) chondrocytes, their relative implications in leukotriene B(4) (LTB(4)) production, the effect of different factors on this system, and the influence of increased LTB(4) production on the synthesis of catabolic factors of cartilage. METHODS: FLAP and 5-LOX expression and LTB(4) production were monitored following treatment with transforming growth factor beta1 (TGFbeta1; 5 ng/ml) and 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3); 50 nM) alone or in combination with selective or nonselective cyclooxygenase (COX) inhibitors, naproxen (90 mug/ml), NS-398 (10 muM), or FR122047 (5 muM), or a dual inhibitor of COX/5-LOX activity, licofelone (2.6 muM). LTB(4), prostaglandin E(2) (PGE(2)), and matrix metalloprotease 1 (MMP-1) production were measured by specific enzyme-linked immunosorbent assays, nitric oxide by the Griess reaction, and FLAP and 5-LOX expression by quantitative polymerase chain reaction. RESULTS: Human OA chondrocytes expressed both FLAP and 5-LOX. TGFbeta1 and/or 1,25(OH)(2)D(3) induced a rapid and marked enhancement ( approximately 4-13-fold) in FLAP messenger RNA (mRNA) levels, which was associated with a subsequent and late increase in LTB(4) production and PGE(2) synthesis. Treatment with COX inhibitors in the absence or presence of TGFbeta1 and 1,25(OH)(2)D(3) induced a rapid increase in LTB(4) production; this response was mediated by the sustained and significant (P < 0.01) up-regulation ( approximately 1.5-fold) of 5-LOX mRNA levels. Conversely, treatment with licofelone showed no effect on 5-LOX but significantly reduced FLAP expression levels. Coincubation of licofelone with TGFbeta1 plus 1,25(OH)(2)D(3) did not affect FLAP or 5-LOX levels. In the presence of TGFbeta1 plus 1,25(OH)(2)D(3), naproxen, but not licofelone, induced MMP-1 production and both drugs decreased nitric oxide levels. CONCLUSION: Both the eicosanoids PGE(2) and LTB(4) are important cofactors in regulating FLAP/5-LOX expression; the inhibition of PGE(2) up-regulates 5-LOX while down-regulating FLAP gene expression, and LTB(4) appears to be an up-regulating factor on the 5-LOX gene. Importantly, nonsteroidal antiinflammatory drugs up-regulate the synthesis of LTB(4), supporting the shunt hypothesis from COX to 5-LOX. We also demonstrated that LTB(4) likely contributes to the up-regulation of important catabolic factors involved in the pathophysiology of OA, such as MMP.

5-Lipoxygenase-Activating Proteins↗
PubMed2004

Anterior femoroacetabular impingement: part I. Techniques of joint preserving surgery.

The exact pathomechanism responsible for osteoarthritis (OA) of the nondysplastic hip has remained unknown for many years. There is, however, emerging clinical evidence implicating femoroacetabular impingement as an etiologic factor for having early OA of the hip develop. Femoroacetabular impingement is an abutment conflict occurring between the proximal femur and the acetabular rim arising from morphologic abnormalities affecting the acetabulum or the proximal femur, or both. The repetitive mechanical conflict occurring during motion, particularly flexion and internal rotation, can lead to lesions of acetabular labrum and, even more serious, the adjacent acetabular cartilage. Surgical treatment of femoroacetabular impingement focuses on improving the clearance for hip motion and alleviation of femoral abutment against the acetabular rim. We will describe the rationale for the treatment of this condition, and discuss the technique of joint-preserving surgery.

Acetabulum↗