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Biomedical subjects

Jean-Philippe Hauzeur

Publications and source records attributed to Jean-Philippe Hauzeur.

8 recordsLinked to original sources
PubMed2006

Peroxisome proliferator-activated receptor-gamma1 is dephosphorylated and degraded during BAY 11-7085-induced synovial fibroblast apoptosis.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a central role in whole body metabolism by regulating adipocyte differentiation and energy storage. Recently, however, PPAR-gamma has also been demonstrated to affect proliferation, differentiation, and apoptosis of different cell types. As we have previously shown that BAY 11-7085-induced synovial fibroblast apoptosis is prevented by PPAR-gamma agonist 15d-PGJ2; the expression of PPAR-gamma in these cells was studied. Both PPAR-gamma1 and PPAR-gamma2 isoforms were cloned from synovial fibroblast RNA, but only PPAR-gamma1 was detected by Western blot, showing constitutive nuclear expression. Within minutes of BAY 11-7085 treatment, a PPAR-gamma1-specific band was shifted into a form of higher mobility, suggesting dephosphorylation, as confirmed by phosphatase treatment of cell extracts. Of interest, BAY 11-7085-induced PPAR-gamma1 dephosphorylation was followed by PARP and caspase-8 cleavage as well as by PPAR-gamma1 protein degradation. PPAR-gamma1 dephosphorylation was followed by the loss of PPAR-DNA binding activity ubiquitously present in synovial fibroblast nuclear extracts. Unlike the phosphorylated form, dephosphorylated PPAR-gamma1 was found in insoluble membrane cell fraction and was not ubiquitinated before degradation. PPAR-gamma1 dephosphorylation coincided with ERK1/2 phosphorylation that accompanies BAY 11-7085-induced synovial fibroblasts apoptosis. 15d-PGJ2, PGD2, and partially UO126, down-regulated ERK1/2 phosphorylation, protected cells from BAY 11-7085-induced apoptosis, and reversed both PPAR-gamma dephosphorylation and degradation. Furthermore, PPAR-gamma antagonist BADGE induced PPAR-gamma1 degradation, ERK1/2 phosphorylation, and synovial fibroblasts apoptosis. The results presented suggest an anti-apoptotic role for PPAR-gamma1 in synovial fibroblasts. Since apoptotic marker PARP is cleaved after PPAR-gamma1 dephosphorylation but before PPAR-gamma1 degradation, dephosphorylation event might be enough to mediate BAY 11-7085-induced apoptosis in synovial fibroblasts.

Apoptosis↗
PubMed2005

Stem cell therapy for osteonecrosis of the femoral head.

Aseptic non-traumatic osteonecrosis of the femoral head is a painful disorder of the hip that can lead to femoral head collapse and the need for total hip replacement. As osteonecrosis may be a disease of mesenchymal cells or bone cells, the possibility has been raised that bone marrow containing osteogenic precursors implanted into the necrotic lesion could be of benefit in this condition. Indeed, bone marrow contains adult stem cells, such as haematopoietic stem cells, mesenchymal stem cells and multipotent stem cells, that might have osteogenic properties. The efficacy of bone marrow implantation into the osteonecrotic zone was studied in two prospective trials. This treatment avoided the progression of the disease to the stage of the subchondral fracture (stage III) and reduced the need for total hip replacement. The mechanisms involved might include improved osteogenesis and angiogenesis. This new therapeutic approach should modify the treatment of early-stage osteonecrosis of the femoral head.

Femur Head Necrosis↗
PubMed2005

Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. Surgical technique.

BACKGROUND: Aseptic nontraumatic osteonecrosis of the femoral head is a disorder that can lead to femoral head collapse and the need for total hip replacement. Since osteonecrosis may be a disease of mesenchymal cells or bone cells, the possibility has been raised that bone marrow containing osteogenic precursors implanted into a necrotic lesion of the femoral head may be of benefit in the treatment of this condition. For this reason, we studied the implantation of autologous bone-marrow mononuclear cells in a necrotic lesion of the femoral head to determine the effect on the clinical symptoms and the stage and volume of osteonecrosis. METHODS: We studied thirteen patients (eighteen hips) with stage-I or II osteonecrosis of the femoral head, according to the system of the Association Research Circulation Osseous. The hips were allocated to a program of either core decompression (the control group) or core decompression and implantation of autologous bone-marrow mononuclear cells (the bone-marrow-graft group). Both patients and assessors were blind with respect to treatment-group assignment. The primary outcomes studied were safety, clinical symptoms, and disease progression. RESULTS: After twenty-four months, there was a significant reduction in pain (p = 0.021) and in joint symptoms measured with the Lequesne index (p = 0.001) and the WOMAC index (p = 0.013) within the bone-marrow-graft group. At twenty-four months, five of the eight hips in the control group had deteriorated to stage III, whereas only one of the ten hips in the bone-marrow-graft group had progressed to this stage. Survival analysis showed a significant difference in the time to collapse between the two groups (p = 0.016). Implantation of bone-marrow mononuclear cells was associated with only minor side effects. CONCLUSIONS: Implantation of autologous bone-marrow mononuclear cells appears to be a safe and effective treatment for early stages of osteonecrosis of the femoral head. Although the findings of this study are promising, their interpretation is limited because of the small number of patients and the short duration of follow-up. Further study is needed to confirm the results.

Bone Marrow Transplantation↗
PubMed2004

Melorheostosis with bilateral involvement in a black African patient.

Melorheostosis is a rare chronic bone disease of unknown etiology that often affects a single limb. Onset usually occurs in childhood or early adolescence. A flowing wax appearance along the surface of the bone and multiple areas of bone sclerosis produce a typical radiographic picture. We describe the first case reported in a black African, in whom an exceedingly rare feature was a bilateral distribution of the lesions.

Africa↗
PubMed2004

Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study.

BACKGROUND: Aseptic nontraumatic osteonecrosis of the femoral head is a disorder that can lead to femoral head collapse and the need for total hip replacement. Since osteonecrosis may be a disease of mesenchymal cells or bone cells, the possibility has been raised that bone marrow containing osteogenic precursors implanted into a necrotic lesion of the femoral head may be of benefit in the treatment of this condition. For this reason, we studied the implantation of autologous bone-marrow mononuclear cells in a necrotic lesion of the femoral head to determine the effect on the clinical symptoms and the stage and volume of osteonecrosis. METHODS: We studied thirteen patients (eighteen hips) with stage-I or II osteonecrosis of the femoral head, according to the system of the Association Research Circulation Osseous. The hips were allocated to a program of either core decompression (the control group) or core decompression and implantation of autologous bone-marrow mononuclear cells (the bone-marrow-graft group). Both patients and assessors were blind with respect to treatment-group assignment. The primary outcomes studied were safety, clinical symptoms, and disease progression. RESULTS: After twenty-four months, there was a significant reduction in pain (p = 0.021) and in joint symptoms measured with the Lequesne index (p = 0.001) and the WOMAC index (p = 0.013) within the bone-marrow-graft group. At twenty-four months, five of the eight hips in the control group had deteriorated to stage III, whereas only one of the ten hips in the bone-marrow-graft group had progressed to this stage. Survival analysis showed a significant difference in the time to collapse between the two groups (p = 0.016). Implantation of bone-marrow mononuclear cells was associated with only minor side effects. CONCLUSIONS: Implantation of autologous bone-marrow mononuclear cells appears to be a safe and effective treatment for early stages of osteonecrosis of the femoral head. Although the findings of this study are promising, their interpretation is limited because of the small number of patients and the short duration of follow-up. Further study is needed to confirm the results.

Adult↗
PubMed2003

Sonography detection threshold for knee effusion.

The aim of this study was to determine the threshold for detecting knee effusion by ultrasound (US). Five knee specimens from embalmed cadavers were studied. Intra-articular injection of saline, blood and synovial fluid was performed under ultrasound control and methylene blue dye instillation. The smallest amount of fluid detectable by US in the knee was 7.4 ml for synovial fluid, 10.1 and 10.4 ml for saline solution and 9.7 for blood. The threshold for detecting knee joint effusion by US in cadaver specimens was 10 ml for saline and blood and 7 ml for synovial fluid.

Cadaver↗
PubMed2003

Abnormalities in the replicative capacity of osteoblastic cells in the proximal femur of patients with osteonecrosis of the femoral head.

OBJECTIVE: Aseptic nontraumatic osteonecrosis (ON) of the femoral head is a painful disorder that often leads to femoral head collapse due to subchondral fracture. We postulated that alteration of osteoblast function might play a role in the pathophysiology of ON. We evaluated the ex vivo proliferation rate and differentiation capacity of osteoblasts derived from the intertrochanteric region of the femur and of the iliac crest of patients with ON of the femoral head and compared it with patients with hip osteoarthritis (OA). METHODS: We examined the function of osteoblastic cells in cultures derived from bone biopsies of the intertrochanteric region of the femur and of the iliac crest obtained from 13 patients with ON of the femoral head and 8 patients with hip OA. The replicative capacity was assessed by the proliferation rate in secondary culture. The phenotypic characterization was evaluated by the level of alkaline phosphatase activity, the sensitivity to 1,25 (OH)2 vitamin D3, and collagen synthesis. RESULTS: The replicative capacity of the osteoblastic cells of the intertrochanteric area of the femur in ON patients was significantly reduced compared to patients with OA. The capacity of differentiation, however, was not different between ON and OA patients. CONCLUSION: The replicative capacity of osteoblastic cells is significantly reduced in the femur of patients with ON. Our results confirm that altered osteoblastic function plays a role in the pathophysiology of ON of the femoral head.

Adult↗