The incidence of acetabular osteolysis in young patients with conventional versus highly crosslinked polyethylene.

BACKGROUND: Osteolysis is a major mode of hip implant failure. Previous literature has focused on the amount of polyethylene wear comparing highly crosslinked polyethylene (HXPLE) with conventional liners but has not clarified the relative incidence of osteolysis with these two liners. QUESTIONS/PURPOSES: We determined (1) the incidence of osteolysis in HXLPE versus conventional polyethylene (CPE), (2) the ability to detect and evaluate the size of lytic lesions using radiographs compared with CT scans, (3) head penetration in hips without and with lysis, and (4) determined whether acetabular position, head size, and UCLA activity score contributed to lysis. METHODS: We compared head penetration and osteolysis on plain radiographs and presence and volume of osteolysis on CT scans in 48 patients with HXLPE (mean, 46.5 years) and 50 patients with CPE (mean, 43.2 years). The minimum followup was 5 years (average, 7.2 years; range, 5.1-10.9 years), RESULTS: Osteolysis was apparent on CT in a larger number of patients with CPE liners than HXLPE liners: 12 of 50 (24%) versus one of 48 (2%), respectively. We found no correlation between head penetration and volume of osteolytic lesions. Head penetration was greater in patients with osteolysis. Smaller head sizes were associated with greater wear and those with osteolysis had smaller head sizes; however, there was no difference in acetabular component position or UCLA activity in those with lysis compared with those without. CONCLUSIONS: HXLPE diminished the incidence of osteolysis, but the lack of correlation between penetration and volume of osteolysis suggests other factors other than wear contribute to the development of osteolysis. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The p33ING1b tumor suppressor cooperates with p53 to induce apoptosis in response to etoposide in human osteosarcoma cells.

p33ING1b induces cell cycle arrest and stimulates DNA repair, apoptosis and chemosensitivity. The magnitude of some p33ING1b effects may be due to activation of the tumor suppressor p53. To investigate if the p33ING1b protein affected chemosensitivity of osteosarcoma cells, we overexpressed p33ING1b in p53+/+ U2OS cells or in p53-mutant MG63 cells, and then assessed for growth arrest and apoptosis after treatment with etoposide. p33ING1b increased etoposide-induced growth inhibition and apoptosis to a much greater degree in p53+/+ U2OS cells than in p53-mutant MG63 cells. Moreover, ectopic expression of p33ING1b markedly upregulated p53, p21WAF1 and bax protein levels and activated caspase-3 protein kinase in etoposide-treated U2OS cells. Together, our data indicate that p33ING1b prominently enhances etoposide-induced apoptosis through p53-dependent pathways in human osteosarcoma cells. p33ING1b may be an important marker and/or therapeutic target in the prevention and treatment of metastatic osteosarcoma.

The tumor suppressor p33ING1b enhances taxol-induced apoptosis by p53-dependent pathway in human osteosarcoma U2OS cells.

p33ING1b can stimulate cell cycle arrest, DNA repair, apoptosis and chemosensitivity. The actions of p33ING1b involve p53-dependent and p53-independent mechanisms. To investigate if the p33ING1b isoform is involved in the chemosensitivity of osteosarcoma cells, p33ING1b was overexpressed in p53+/+ U2OS cells or p53-mutant MG63 cells, and then cell growth arrest and apoptosis were assessed after treatment with taxol. The results showed that p33ING1b markedly increased taxol-induced growth inhibition and apoptosis in p53+/+ U2OS cells, but not in p53-mutant MG63 cells. Moreover, ectopic expression of p33ING1b could obviously upregulate p53, p21WAF1 and bax protein levels and activate caspase-3 in taxol-treated U2OS cells. Taken together, our data demonstrate that p33ING1b enhances taxol-induced apoptosis through p53-dependent pathway in human osteosarcoma cells. p33ING1b may be an important marker and/or therapeutic target in the prevention and treatment of osteosarcoma.

[p33(ING1b) enhances chemosensitivity of osteosarcoma cell U2OS to etoposide].

BACKGROUND & OBJECTIVE: As a new tumor suppressor gene, ING1 shared many biological functions with p53, such as cell cycle arrest, DNA repair, apoptosis, and chemosensitivity. The aim of this study was to investigate the effect of p33(ING1b) on chemosensitivity of osteosarcoma cells and its mechanism. METHODS: p33(ING1b) was overexpressed in osteosarcoma cell line U2OS through transient transfection. After transfection, U2OS cells were treated with etoposide for 24 hours, then cell growth inhibitory rates were detected by trypan blue exclusion assay, and apoptosis was assessed using flow cytometry analysis and fluorescent microscopy. Furthermore, the protein expression of p53, p21(WAF1), MDM2 and Bax were determined by Western blot analysis. RESULTS: After transient transfection with p33(ING1b) vector for 24 hours, U2OS cells were treated with 20 microg/ml VP-16 for 24 hours. The results showed that the cell growth inhibitory rates strongly increased [(63.1+/-5.1)%], and etoposide- induced apoptosis was increased(62.7%). Ectopic overexpression of p33(ING1b) increased the protein expression of p53 and strongly enhanced the expression of endogenous p21(WAF1) and Bax. Moreover, after transfection and treatment with 20 microg/ml VP-16, the protein expression of p53, p21(WAF1), and Bax strongly increased compared with other groups. The protein expression of MDM2 showed no significant difference. CONCLUSION: These observations suggest that p33(ING1b) up-regulates p53 protein, and cooperate with p53 in stimulating expression of p21(WAF1) and Bax gene, thus to enhance etoposide-induced apoptosis via p53-dependent pathways.