Onset Of Osteolysis Research Articles

MALAT1 enhanced the proliferation of human osteoblasts treated with ultra‑high molecular weight polyethylene by targeting VEGF via miR‑22‑5p.

Osteolysis associated with an implanted prosthesis is the major cause of failure in prosthesis implantation, and a severe public health issue worldwide. The type of bone metabolism associated with this disorder has been a major focus for improving the outcomes of patients with osteolysis. The role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1; a member of the long coding RNA family) during the onset of osteolysis and the related molecular regulatory mechanism in ultra-high molecular weight polyethylene (UHMWPE)-treated hFOB 1.19 cells were investigated in the current study. The effect of MALAT1 knockdown on cell viability, cell apoptosis and osteolysis-associated signaling were also examined, and the interactions that occurred between MALAT1 and an anti-osteolysis molecule, microRNA (miR)-22-5p were investigated. Additionally, knockdown of vascular endothelial growth factor (VEGF) exerted similar biological effects as observed following miR-22-5p overexpression. The data showed that MALAT1 and pro-osteolysis indicators, receptor activator of nuclear factor-κB ligand (RANKL) and VEGF were upregulated in clinical interface membrane samples. Knockdown of MALAT1 inhibited the growth of UHMWPE-treated hFOB 1.19 cells, and this effect was associated with the upregulation of OPG, and downregulation of RANKL and VEGF. Results of a dual luciferase assay confirmed the interaction between VEGF and miR-22-5p, and also between MALAT1 and miR-22-5p. Additionally, subsequent assays indicated that overexpression of MALAT1 suppressed the anti-osteolysis effect of miR-22-5p, which would further induce VEGF expression. The data indicated that MALAT1 has an in port ant role in the onset of osteolysis via its ability to induce RANKL expression and inhibit the effect of miR-22-5p.

The implication of the osteolysis threshold and interfacial gaps on periprosthetic osteolysis in cementless total hip replacement

Osteolysis around joint replacements may develop due to migration of wear particles from the joint space into gaps between the interface bone and the implant where they can accumulate in high concentrations to cause tissue damage. Osteolysis may appear in various postoperative times and morphological shapes which can be generalized into linear and focal. However, there are no clear explanations on the causes of such variations. Patients’ degree of sensitivity to polyethylene particles (osteolysis thresholds), the local particle concentration and the access route provided by the interface gaps have been described as determining factors. To study their effects, a 2D computational fluid dynamics model of the hip joint capsule in communication with an interfacial gap and the surrounding bone was employed. Particles were presented using a discrete phase model (DPM). High capsular fluid pressure was considered as the driving force for particle migration. Simulations were run for different osteolysis thresholds ranging from 5×108 to 1×1012 particle number per gram of tissue and fibrous tissue generation in osteolytic lesion due to particles was simulated for the equivalent of ten postoperative years. In patients less sensitive to polyethylene particles (higher threshold), osteolysis may be linear and occur along an interfacial gap in less than 5% of the interfacial tissue. Focal osteolysis is more likely to develop in patients with higher sensitivity to polyethylene particles at distal regions to an interfacial gaps where up to 80% of the interfacial tissue may be replaced by fibrous tissue. In these patients, signs of osteolysis may also develop earlier (third postoperative year) than those with less sensitivity who may show very minor signs even after ten years. This study shows the importance of patient sensitivity to wear particles, the role of interfacial gaps in relation to morphology and the onset of osteolysis. Consequently, it may explain the clinically observed variation in osteolysis development.

Measurement of tumor load and distribution in a model of cancer-induced osteolysis: a necessary precaution when testing novel anti-resorptive therapies.

The Arguello model of cancer metastasis to bone has been used extensively to study breast cancer-induced osteolytic disease. The effects of therapy on skeletal disease and on tumour burden in soft organs are traditionally measured using radiography and/or time-consuming histomorphometry, respectively. The purpose of this study was to develop a sensitive and efficient method for evaluating tumour burden in vivo using MDA-231 cells transduced with the E. coli lacZ gene (MDA-231BAG). Osteolysis was measured by radiography and tumour burden was measured histomorphometrically or biochemically. In untreated mice, measurements of tumour burden in bone extracts using human cytokeratin-associated tissue polypeptide antigen (TPA) ELISA or E. coli beta-galactosidase (beta-gal) activity immunoassay reflected the extent of osteolytic disease as measured by radiography; however, tumour load could be detected before onset of osteolysis. When monitoring the effect of therapy (0.2 mg/kg ibandronate/day), radiography alone proved to be insufficient. Mice treated with the bisphosphonate ibandronate from time of inoculation with cancer cells had no radiologically visible signs of osteolysis but significant tumour load was measured in the bone extracts using these assays. Furthermore, beta-gal activity could be used as a measurement of tumour load in soft organs, and unlike other human breast cancer markers expressed by the MDA-231 cells in vitro, beta-gal activity was detected in the serum of mice with progressive disease. In conclusion, we describe an efficient model of breast cancer-induced osteolysis to quantify the effect of therapy on disease load and distribution, which could be beneficial in evaluating novel therapies for the treatment of the disease.

セメントレスＴＨＡの中期成績

The results of fifty-five cementless total hip arthroplasties using the Omniflex system were reviewed. All patients were followed clinically and radiographically for more than four years.The AD stem (non-HA stem) was used from January 1993 to October 1995, and the Securflex (HA stem) was used from November 1995 to December 1996.On the stem side, five unstable fixation stems were observed in the non-HA group. In the HA group, we found early osseointegration in all cases. On the socket side, there were no loose shells.We need to observe osteolysis carefully since the onset of osteolysis seems to increase gradually with polyethylene wear.