Objective To compare the effectiveness and linear wear rates between high cross-linked polyethylene cup liner and traditional polyethylene cup liner. Methods A retrospective analysis was made on the clinical data of 61 patients (64 hips) who underwent primary total hip arthroplasty (THA) between January 2005 and March 2007. According to the type of cup liner, 61 patients (64 hips) were divided into 2 groups: high cross-linked polyethylene cup liner was used in 30 cases (31 hips, trial group), and traditional polyethylene cup liner in 31 cases (33 hips, control group). There was no significant difference in gender, age, body weight, etiological factor, and preoperative Harris score between 2 groups (P gt; 0.05). Complication was observed after operation; Harris score was used to assess hip function; X-ray film analysis was done to observe osteolysis and prosthesis loosening, and to measure cumulative penetration of the femoral head and linear wear rate. Results All incisions healed by first intention without complication. All patients were followed up. The mean follow-up was 6.3 years (range, 5-7 years) in trial group, and was 6.5 years (range, 4-7 years) in control group. There was no significant difference in Harris score between 2 groups at the 3 months after operation and last follow-up (P gt; 0.05). Osteolysis was observed in 3 cases (3 hips) of control group, but no osteolysis in trial group. X-ray films showed no aseptic loosening in the patients of 2 groups. The mean cumulative penetration of trial group were significantly lower than those of control group at 1-7 years after operation (P lt; 0.05). Linear wear rate of trial group [(0.025 ± 0.002) mm/year] was significantly lower than that of control group [(0.086 ± 0.005 ) mm/year] (Z=6.804, P=0.000). Conclusion High cross-linked polyethylene cup liner has the similar effectiveness as traditional polyethylene cup liner, but it has lower linear wear rate than the traditional polyethylene cup liner.
Objective To observe the expressions of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase 9 (MMP-9) around the prosthesis, and to study the relationship between the expressions of EMMPRIN and MMP-9 and osteolysis around prosthesis. Methods Interface tissues were obtained at three Delee-Charnley acetabular sections and seven Gruen femur sections from 8 cases (8 hips) undergoing revision after total hip arthroplasty between February 2010 and January 2012, and were divided into osteolysis group and non-osteolysis group based on preoperative X-ray film and intraoperative observation; the tissues from another 8 patients with osteoarthritis undergoing total hip arthroplasty as the control group. The immunohistochemical staining and RT-PCR assays were used to determine the expressions of EMMPRIN and MMP- 9. The correlation between the positive cells and the severity of osteolysis were analyzed and compared. Results Histological examination showed that many macrophages, multinucleated giant cells assembled in the membrane of osteolysis zone, but many fibroblasts and synovial cells in non-osteolysis zones. EMMPRIN and MMP- 9 positive cells and gene expressions were observed in every group. The percentage of positive cells and gene expression of EMMPRIN and MMP-9 in osteolysis group were significantly higher than those in non-osteolysis and control groups (P lt; 0.05), but no significant difference was found between non-osteolysis group and control group (P gt; 0.05). The percentage of positive cells of EMMPRIN in zone III of acetabular was higher than that in zone I and zone II of revision hip (P lt; 0.05), but no significant difference between zone I and zone II (P gt; 0.05). The percentage of positive cells of MMP-9 in zone I and zone III was significantly higher than that in zone II of revision hip (P lt; 0.05), but no significant difference between zone I and zone III (P gt; 0.05). The expression of EMMPRIN from high to low in order was zones 1, 7, 4, 2, 3, 5, and 6 at femur; the values of zones 1, 7, and 4 were significantly higher than those of zones 2, 3, 5, and 6 (P lt; 0.05), but no significant difference among zones 1, 7, and 4, and among zones 2, 3, 5, and 6 (P gt; 0.05). The expression of MMP-9 from high to low in order was zones 1, 7, 4, 2, 3, 6, and 5 at femur; the values of zones 1 and 7 were significantly higher than those of zones 4, 2, 3, 6, and 5 (P lt; 0.05), and the values of zones 4 and 2 were significantly higher than those of zones 3, 6, and 5 (P lt; 0.05), but no significant difference between zone 1 and zone 7, between zone 4 and zone 2, and among zones 3, 5, and 6 (P gt; 0.05). Conclusion The expressions of EMMPRIN and MMP-9 have certain coherence. The over-expressions of EMMPRIN and MMP-9 may be one of the key points of inhibiting bone reconstruction and bone resorption at bone-implant interface under the stimulation of wear debris．
Objective To investigate the possibility of gene therapy of osteolysis around artificial joint prosthesis by constructing the recombinant adenovirus which can silence tumor necrosis factor α (TNF-α). Methods The primer of small interfering RNA (siRNA) coding sequence of silent TNF-α was designed and amplified, and then RAPAD adenovirus packaging system was used to load the sequence to adenovirus, and the recombinant adenovirus Ad5-TNF-α-siRNA-CMVeGFP which lacked both E1 and E3 regions was constructed. Then 64 female BABL/C mice (weighing, 20-25 g) were randomly divided into 4 groups (n=16): blank control (group A), positive control (group B), simple adenovirus (group C), and treatment group (group D). The prosthetic-model was established in group A, and the prosthetic-loosening-model in groups B, C, and D. At 2 weeks after modeling, PBS solution was injected first, and then the same solution was injected 24 hours later in group A; titanium particle solution was injected, and then PBS solution, Ad5 E1-CMVeGFP (1 × 109 PFU/mL), and Ad5-TNF-α-siRNA-CMVeGFP (1 × 109 PFU/mL) were injected, respectively in groups B, C, and D 24 hours later, every 2 weeks over a 10-week period. The general condition of mice was observed after operation. The tissues were harvested for histological observation, and the expression of TNF-α was detected by Western blot at 12 weeks after operation. Results The positive clones were achieved by enzyme digestion and confirmed by DNA sequencing after loading the target genes into adenovirus vector, and then HEK293 cells were successfully transfected by recombinant adenovirus Ad5-TNF-α-siRNA-CMVeGFP. All mice survived to the completion of the experiment. Histological observation showed that there were few inflammatory cells and osteoclasts in group A, with a good bone formation; there were a large number of inflammatory cells and osteoclasts in groups B and C, with obvious bone destruction; inflammatory cells and osteoclasts in group D was less than those in groups B and C, with no obvious bone destruction. Significant difference was found in the limiting membrane thickness and the number of osteoclasts (group A lt; group D lt; group B lt; group C, P lt; 0.05). Western blot showed that the TNF-α expression levels were 0.235 ± 0.022, 0.561 ± 0.031, 0.731 ± 0.037, and 0.329 ± 0.025 in groups A, B, C, and D respectively, showing significant difference among 4 groups (P lt; 0.05). Conclusion The recombinant adenovirus for silencing TNF-α is successfully constructed, which can effectively inhibit osteolysis by silencing TNF-α expression in the tissues around prosthesis in mice.
Objective To observe the effect of local injection of vascular endothel ial growth factor (VEGF) and VEGF antibody on the wear particle-induced osteolysis in the mouse air pouch model and to investigate the role of VEGF in the process of aseptic loosening of prosthesis. Methods The stem of metal hip prosthesis was obtained from the revision surgery.Metallic wear particles were made by vacuum ball mill ing. Wear particles suspension was prepared into the concentration of 10 mg/mL with PBS. Fifty female Kunming mice (aged 8-10 weeks, weighing about 25 g) were selected. Of 50 mice, 10 were used as the donors of bone graft, the other 40 were equally divided into control group (group A), particle group (group B), VEGF group (group C), and VEGF inhibited group (group D). Air pouches were made on the back of 40 mice by injecting sterile air subcutaneously. At 8th day, a graft of calvaria from the donor mice was implanted in air pouch. In groups B, C, and D, 0.5 mL wear particles suspension was injected into the air pouches, and in group A, 0.5 mL PBS was injected. Once a day at 6th and 7th days during the air pouch preparation and one time every two days after bone implantation, 0.2 mL recombinant human VEGF (rhVEGF) and VEGF antibody (Bevacizumab) were injected into the air pouches in groups C and D, respectively. In group A and group B, 0.2 mL sal ine was injected. Pouch tissues and bone were harvested at 2 weeks after bone implantation for HE staining, real-time fluorescent quantitative PCR and ELISA analyses. Results All mice survived to the end of experiment. The gross observation showed that there were mild redness, swell ing, and less neovascularization in air pouches in group A. There were obvious redness, swell ing, and more exudative and neovascularization in groups B, C, and D, most obvious in group C, the next in group B, then in group D. The histological and molecular biological analysis showed that inflammatory responses and osteolysis were obvious in group B and the pouch membrane thickness, the cell density, transforming growth factor α, interleukin 1β, and VEGF were significantly higher than those in group A (P lt; 0.05). The inflammatory responses and osteolysis were mostobvious in group C and the above-mentioned indexes were significantly higher than those in group B (P lt; 0.05). There were some inflammatory responses and osteolysis in group D, but the indexes were significantly lower than those in group B (P lt; 0.05) and were significantly higher than those in group A (P lt; 0.05). Conclusion VEGF can promote inflammatory responses and osteolysis in aseptic loosening of prosthesis. VEGF antibody can effectively inhibit wear particle-induced osteolysis.
Objective Aseptic loosening of prosthesis is associated with peri prosthetical osteolysis caused by osteoclast activation. Receptor activator of nuclear factor kappa B (NF-κB) l igand (RANKL)/receptor activator of NF-κB (RANK) signalpathway is fundamental in osteoclast activation. To determine whether RANKL antibody can inhibit inflammatory osteolysis in a osteolysis model of mouse. Methods Sixty female BALB/c mice (aged 8-10 weeks, weighing 18-20 g) were selected. The skull bone piece was harvested from 20 mice as the donor of bone graft; the subcutaneous air pouches (2 cm × 2 cm) models were established on the back of the other 40 mice and the skull bone piece was inserted into the air pouches. The 40 mice were equally divided into groups A (negative control group), B (positive control group), C (low-dose RANKL antibody group), and D (high-dose RANKL antibody group). At 1 day after bone graft, 0.5 mL PBS was injected into the pouch of group A, 0.5 mL PBS containing titanium particle into groups B, C, and D. At 2 days before the titanium particle was injected, RANKL antibody (0.1 mL) were injected into the pouch of group C (50 μg/mL) and group D (500 μg/mL), respectively every day for 2 days, and 0.1 mL PBS into groups A and B. At 14 days after bone implantation, the pouchmembranes containing implanted bone were harvested for gross observation and histological analyse. Results All mice survived to the end of experiment, and incisions healed well. The gross observation showed that inflammatory responses, exudation, and vascular proliferation were obvious in group B, and were inconspicuous in groups A, C, and D. The histological analysis showed that significantly more infiltration of inflammatory cells, more obvious bone resorption, more bone collagen loss, and more positive staining area were observed in group B than in groups A, C, and D. There were significant differences in inflammatory cell number, pouch membrane thickness, bone collagen loss, and osteoclast content between group B and groups A, C, and D (P lt; 0.05). Conclusion RANKL antibody can directly blockRANKL/RANK signal pathway, which is an efficient therapy to inhibit bone absorption associated with implant wearing particles.
Objective To evaluate the mechanisms of p42/p44 kinase phosphorylation in cell models and to investigate the effect of simvastatin on the prevention and treatment of aseptic loosening of prosthesis by observing the influence of simvastatin on the levels of tumor necrosis factor α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) of human peri pheral blood mononuclear cell (PBMC) challenged with titanium particles. Methods PBMC from 45 mL peripheral blood of healthy adult voluntary donators, were separated and cultured, and divided into 5 groups according to different culturemedium: group A, PBMC and titanium particles; group B, PBMC and titanium particles with 1 × 10-5 mol/L simvastatin; group C, PBMC and titanium particles with 1 × 10-6 mol/L simvastatin; group D, PBMC and titanium particles with 1 × 10-7 mol/L simvastatin; and group E, PBMC and titanium particles with the extracellular signal-regulated kinase (ERK1/2) inhibitor U0126. The contents of TNF-α and MCP-1 were tested by ELISA after 24 hours of culture. PBMC were pretreated with different medium grouping as groups A, B, C, D, and E for 60 minutes, and were challenged with titanium particles for 30 minutes and 60 minutes, then the level of ERK1/2 expression was tested by Western blot. Results In groups A, B, C, D, and E, the absorbance (A) values of TNF-α were 1.115 5 ± 0.243 6, 0.693 6 ± 0.354 3, 0.695 7 ± 0.387 3, 0.716 4 ± 0.478 9, and 0.263 5 ± 0.101 6, respectively; and the A values of MCP-1 were 1.421 0 ± 0.105 3, 0.915 1 ± 0.411 3, 1.003 5 ± 0.464 2, 1.102 0 ± 0.353 9, and 0.271 3 ± 0.145 1, respectively. The levels of TNF-α and MCP-1 in group A were significantly higher than others, showing significant differences (P lt; 0.05). There were significant differences between group E and groups B, C, and D (P lt; 0.05), between group B and groups C, D (P lt; 0.05); no significant difference between group C and group D (P gt; 0.05). Western blot results showed the expression of ERK1/2 in all groups at 30 minutes and 60 minutes of culture. The levels of ERK1/2 expression were 1.612 1 ± 0.068 2, 1.078 1 ± 0.072 8, 1.268 7 ± 0.223 1, 1.439 7 ± 0.180 1, and 0.732 0 ± 0.110 4 in groups A, B, C, D, and E, respectively; showing significant differences between groups (P lt; 0.05). Conclusion ERK1/2 is a phosphorylated protein after stimulated by wear particles; it is also one of the most important cell signal ing activation of macrophage. Simvastatin can inhibit the expression of bone absorptive factors induced by wear particles and may be used in the prevention and treatment of aseptic loosening of prosthesis.
Objective To observe expression of Caspase-3 and apoptosis around the prosthesis and explore the relationship of the expression and the apoptosis with the periimplant osteolysis. Methods From April 2001 to August 2006, 16 patients (10 males, 6 females) underwent the revision total hip arthroplasty surgery, who had the primary total hip arthroplasty at the ages of 45-67 years and had the revision total hip arthroplasty at the ages of 55-78 years, with the implantation duration of 7-13 years. According to their preoperative X-ray films andthe findings during the operation, the patients were divided into two groups: theloose/osteolytic group (n=8) and the loose/non-osteolytic group (n=8). The interface tissues were obtained from the peri-implant region in the patients. The synovial samples were taken from another 6 patients (2 males, 4 females; age, 54-68years; illness course, 9-15 years), who underwent the primary total hip arthroplasty for osteoarthritis. These 6 patients were used as controls. The tissues were prepared for the immunohistochemical assays to determine the expression of Caspase-3. The TUNEL assays were performed to quantify the apoptotic cells. The quantitative analysis on the positive cells and the correlation with the presence of the particulate wear debris and the severity of osteolysis were also performed. Results The level of the expression for Caspase-3 and the apoptosis index inthe loose/osteolytic group were significantly increased when compared with those in the loose/non-osteolytic group and the control group (P＜0.01). The polyethylene particles were surrounded by more positive cells than the metal particles. The positive cells were present at a higher level in the tissue sections where the high-wear status was present when compared with the areas where the low-wear status was present (P＜0.05). Conclusion There is a statistical correlation of the Caspase-3 expression to the apoptosis index and to the presence of the particulate wear debris and the severity of osteolysis, which may be one of the key points for the bone reconstruction inhibition and the bone resorption at the boneimplant interface under the stimulation of the wear debris. The apoptosis is involved in the pathogenesis of the aseptic loosening, which is closely related to the signal transportation of Caspase-3.
Objective To study the effect of the high molecular weight polyethylene on the periprosthetic tissue in vivo as to give some reference to treatment of loosening hip arthroplasty. Methods Every lower limb of 20 New Zealand white rabbits was implanted a CoCrMo plug in femur by intercondylar notch. 15 mg polyethylene particles, dispersed in 1.5 ml normal saline solution, were injected into one knee joint. The other knee joint was injected 1.5 ml normal saline solution as control. This procedure was repeated 2,4,6,8 and 10 weeks after the implantation. Both of two lower limbs were given a X-ray examination 10 weeks to assess if there were periprosthetic osteolysis and loosening of the plugs. All animals were killed 2 weeks afer the last injection. The distribution of polyethylene in the knee joint capsule was examined to understand if there were loosening of implants or tissue change around implants. Knee joint capsule tissues and periprosthetic tissues were examed by optical microscope. Results Nine cases formed fibrous membrane and four cases formed new bone around prostheses in experiment group. Eleven cases formed new bone and two cases formed fibrous membrane in control group(Plt;0.05)The X-ray results indicated that the plugs were in distal medulla of femur. There was no sign of priprosthetic osteolysis, implants loosening or new bone formation. Optical microscope study indicated that there were a lot of polyethylene particles inside the capsule. The polythlene particles were surrounded by multinucleated foreignbody giant cells and fibrobast. In some cases, there were fibroblasts and fibrous tissue around plug. There were no polyethylene paticles and multinucleated foreignbody giant cells around plug in the marrow. There were alot of polyehtlene particles on the joint surface. The bone surface that contacted multinucleated foreignbody giant cells was coarse. Conclusion Maximing ultra high molecular weight polyethylene can restrain rabbit periprosthetic bone formation
ObjectiveTo analyze the mid-and long-term effectiveness of the 3rd-generation ceramic-on-ceramic (CoC) total hip arthroplasty (THA) in the younger patients. MethodsA retrospective analysis was made on the clinical data of 68 younger patients (73 hips) who accepted the 3rd-generation CoC THA between March 2001 and May 2009. Of 68 cases, 39 was male and 29 was female with the average age of 38.6 years (range, 18-50 years); there were 15 cases (15 hips) of osteonecrosis of the femoral head, 9 cases (9 hips) congenital dysplasia of the hip, 5 cases (8 hips) of ankylosing spondylitis, 10 cases (10 hips) of osteoarthritis of the hip joint, 12 cases (12 hips) of traumatic hip arthritis, 12 cases (12 hips) of femoral neck fracture, 4 cases (6 hips) of rheumatoid hip arthritis, and 1 case (1 hip) of tumor of the femoral neck. The Harris score and University of California Los Angeles (UCLA) score were used to evaluate the hip joint function and activity level respectively. The visual analogue scale (VAS) was used to assess postoperative thigh pain. Radiological signs of osteolysis, loosening, and alumina ceramic related complications were evaluated continuously. And the KaplanMeier survival analysis was used to assess the prosthesis survival. ResultsThe average duration of follow-up was 9.7 years (range, 6-14 years). Sandwich ceramic liners fracture was observed in 3 cases (3 hips), and revision was performed; 1 case had "squeaking" hip because of physical activity. At last follow-up, Harris score and UCLA score were significantly improved when compared with preoperative scores (P<0.05). Bony healing was obtained in all patients, without osteolysis, loosening, and thigh pain. The VAS score was 0. The 5-year and 10-year cumulative survival rates for ceramic fracture revision were 98.6% and 95.9%, and the 5-year and 10-year cumulative survival rates for osteolysis and loosening revision both were 100%. ConclusionThe 3rd-generation CoC prosthesis offer an excellent option for younger patients in THA and the mid-and long-term effectiveness are satisfactory.
Chloride voltage-gated channel 7 (CLCN7) gene mutations can cause the disorder of acidification in lacunas and osteolysis, leading to osteopetrosis characterized by increased bone density throughout the body and lysosomal storage diseases. Deafness can be caused by nerve injury for bone compression, negative pressure in the middle ear and otosclerosis. This article will introduce structure and function of CLCN7 gene and CLCN7 protein, osteolysis process, including the introduction of osteoclasts and the mechanism of osteolysis, osteopetrosis, mechanism and treatment of osteopetrosis caused by CLCN7 gene mutations, as well as osteopetrosis and syndromic deafness, in order to provide a basis for clinical diagnosis and treatment.