Polyphyllin I alleviates osteoblasts injuries induced by TCP wear particles in vitro via inhibition of autophagy / 中草药

Objective: To observe the effect of polyphyllin I (PPI) on osteoblasts injuries induced by tricalcium phosphate (TCP) wear particles in vitro, and explain its regulation mechanisms. Methods: Primary osteoblasts obtained from the calvaria of neonatal SD rat by the series of digestion were identified with ALP staining. The osteoblasts were treated with TCP wear particles (TCP, 0.1 mg/mL) for 48 h to establish an in vitro injuries model of the calvarial osteoblasts. The experiment was randomly divided into control group, model (TCP, 0.1 mg/mL) group, PPI (30 μg/mL) group and PPI (100 μg/mL) group. CCK-8 and chemical colorimetry were used to examine cell viability and lactic dehydrogenase (LDH) content in culture media; Real-time PCR was performed to detect mRNA levels of ALP, Collagen I and RUNX2 in osteoblasts; The flow cytometry was used to examine apoptosis of osteoblasts using Annexin V/PI double staining; When the osteoblasts were treated for 14 d, mineral nodules formation was observed with alizarin S staining; Western blot was applied to examine proteins expression of Bax, Bcl-2, cleaved Caspase-3, Atg5, p62, and microtubule associated protein 1 light chain3 (LC-3). Results: Compared with control group, model group showed that the cell viability of osteoblasts, mRNA levels of ALP, Collagen I and RUNX2, and mineral nodules formation were significantly decreased; LDH content, percentage of apoptosis and proteins expression of Bax, cleaved Caspase-3, Atg5, LC-3 and the ratio of LC-3II/LC-3I were obviously increased in calvarial osteoblasts, whereas proteins expression of Bcl-2 and p62 was remarkably decreased. Compared with model group, PPI groups indicated that cell viability of osteoblasts, mRNA levels of ALP, Collagen I and RUNX2, and mineral nodules formation were dramatically increased; LDH content, percentage of apoptosis, protein expressions of Bax, cleaved Caspase-3, Atg5, and LC-3 and the ratio of LC-3II/LC-3I were obviously decreased, but Bcl-2 and p62 expression were obviously increased. Conclusion: PPI alleviates osteoblasts injuries induced by TCP wear particles via inhibition of autophagy.

Establishment of artificial joint aseptic loosening mouse model by cobalt-chromium particles stimulation / 中国修复重建外科杂志

Objective: To explore the feasibility of establishment of a artificial joint aseptic loosening mouse model by cobalt-chromium particles stimulation. Methods: Twenty-four 8-week-old male severe combined immunodeficient (SCID) mice were divided into experimental group ( n=12) and control group ( n=12). The titanium nail was inserted into the tibial medullary cavity of mouse in the two groups to simulate artificial joint prosthesis replacement. And the cobalt-chromium particles were injected into the tibial medullary cavity of mouse in experimental group. The survival of the mouse was observed after operation; the position of the titanium nail and the bone mineral density of proximal femur were observed by X-ray film, CT, and Micro-CT bone scanning; and the degree of dissolution of the bone tissue around the tibia was detected by biomechanical test and histological staining. Results: Two mice in experimental group died, and the rest of the mice survived until the experiment was completed. Postoperative imaging examination showed that there was no obvious displacement of titanium nails in control group, and there were new callus around the titanium nails. In experimental group, there was obvious osteolysis around the titanium nails. The bone mineral density of the proximal tibia was 91.25%±0.67%, and the maximum shear force at the tibial nail-bone interface was (5.93±0.85) N in experimental group, which were significantly lower than those in control group [102.07%±1.87% and (16.76±3.09) N] ( t=5.462, P=0.041; t=3.760, P=0.046). Histological observation showed that a large number of inflammatory cells could be seen around the titanium nails in experimental group, while there was no inflammatory cells, and obvious bone tissue formation was observed in control group. Conclusion: The artificial joint aseptic loosening mouse model can be successfully established by cobalt-chromium particles stimulation.

Effect of psoralen on rat osteoblasts injuries induced by TCP wear particles in vitro and its mechanism / 中国应用生理学杂志

To investigate the effect and mechanism of psoralen on calvarial osteoblasts injuries caused by tricalcium phosphate (TCP) wear particles in vitro. Primary osteoblasts were obtained from the calvaria of neonatal SD rat by the series of digestion and were identified with ALP staining. Calvarial osteoblasts were treated with TCP wear particles for 48 h to establish the in vitro model of osteoblasts injuries. The rat osteoblasts were randomly divided into control group, TCP wear particles (0.1 mg/ml) group, psoralen treated (at the concentrations of 10, 10, 10 mol/L) groups. WST assay and the flow cytometry were used to detect the cell viability of osteoblasts and apoptosis, respectively. Chemical colorimetry was performed to examine ALP activity of osteobalsts. When the osteoblasts were treated for 14 day, mineral nodules formation was observed with alizarin red S staining. Western blot was applied to examine protein expressions of glucose regulated protein78/94(GRP78/94), inositol dependent enzyme 1 alpha (IREα), spliced X-box binding protein 1 (XBP1s) and phosphorylated c-Jun N-terminal kinase (p-JNK) in calvarial osteoblasts. Compared with control group, the cell viability of osteoblasts, ALP activity and mineral nodules formation in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and protein expressions of GRP78/94, IRE1α, XBP1 and p-JNK were obviously increased in calvarial osteoblasts (P＜0.05). Compared with TCP group, the injuries of calvarial osteoblasts and cell apoptosis in psoralen treated groups were obviously decreased (P＜0.05), and the expression levels of GRP78/94, IRE1α, XBP1 and p-JNK were down-regulated remarkably (P＜0.05). Psoralen prevents osteoblasts injuries caused by TCP wear particles through IRE1α-XBP1s-JNK signaling pathway activation.

Fractal Characterization and Classification Characteristics of the Artificial Joint Wear Particles / 医用生物力学

Objective To study the morphology and fractal characterization of UHMWPE wear particles by simulation experiment on knee joint, analyze the classification characteristics of wear particles and discuss the correlation between fractal dimension and wear state. Methods The knee joint simulator was used to realize the knee joint wear motion. The forged CoCrMo alloy and UHMWPE were selected as artificial joint prosthesis materials. The wear particle extraction was based on ISO 17853. The automatic extraction and fractal identification system of wear particles were used to investigate fractal characteristics of wear particles. Three kinds of models were established to classify and recognize wear particles, by using the meshing method, cluster analysis and genetic simulated annealing algorithm, respectively. Results The fractal characteristics of UHMWPE single wear particles was very obvious. The fractal dimension calculated by radar fractal method decreased, during the transition from the larger size of strip debris to the smaller size of roundness debris, and the fractal dimension D of spherical debris was close to zero. The weighted sum of squared error values of fractal dimension for wear particle population classification was the smallest by the model of genetic simulated annealing algorithm, and the clustering feature was very obvious. When the wear cycles were low, the large fractal dimension of strip, needle and fibrous abrasive debris with larger fractal dimension had the largest proportion, and the main abrasion modes were the ploughing and spalling wears. With the extension of wear period, the proportion of wear particles with large fractal dimension decreased, and the proportion of flaky, blocky and near-spherical wear particles with low fractal dimension increased clearly. The wear mechanism changed to the fatigue and adhesive wear, and the wear state transited to the composite wear period. During the stable wear period, the proportion of all kinds of abrasive grains changed little. Due to the increase in the number of small particles, the fractal dimension decreased in stable wear state. Conclusions Based on the improved radar graph method, the fractal dimension of wear particles with different profiles could be obtained by automatic extraction and fractal identification system of wear particles. The research findings can be used in shape extraction, fractal dimension calculation and parameter statistics, as well as providing a new digital analysis tool for identification and diagnosis for wear particles of artificial prosthesis.

TCP wear particles causes injury of periprosthetic osteocytes in the mouse calvaria / 中国应用生理学杂志

OBJECTIVE@#To study whether tricalcium phosphate(TCP) wear particles cause injuries of periprosthetic osteocytes in the mouse calvaria, and to explain its molecular mechanism.@*METHODS@#Thirty six-week(ICR)male mice were randomly divided into sham group, model (TCP) group and 3-methyladenine (3-MA) group. A murine calvarial model of osteolysis was established by 30 mg of TCP wear particles implantation over the periosteum around the middle suture of calvaria in mice. On the second postoperative day, the autophagy specific inhibitor 3-MA (1.0 mg/kg) was subcutaneously injected to the calvaria in the 3-MA-treated mice every other day. After 2 weeks, blood and the calvaria were obtained. Micro-CT was used to detect bone mineral density(BMD), bone volume fraction (BVF) and porosity number. HE staining and flow cytometry were performed to analyze the viability and apoptosis of periprosthetic osteocytes. The serum levels of dentin matrix protein 1(DMP-1) and sclerostin (SOST) were determined by ELISA. The proteins expressions of DMP-1, SOST, Beclin-1 and microtuble-associated protein 1 light chain 3 (LC-3) were detected by Western blot in the calvaria osteocytes.@*RESULTS@#Compared with the sham group, the mice in the TCP group showed that a significant decrease in the viability of periprosthetic osteocytes, but obvious increases in number of osteocytes death and osteocytes apoptosis (<0.05), and in serum level and protein expression of SOST; significant decreases in serum level and protein expression of DMP-1 (<0.05), and remarkable up-regulation of autophagy-related factors beclin-1 and the conversion of LC3-Ⅱ from LC3-I in the calvaria osteocytes. Compared with TCP group, the mice in the 3-MA group showed that injuries of calvaria osteocytes were obviously aggravated, and osteocytes apoptosis was significantly increased (<0.05).@*CONCLUSIONS@#TCP wear particles can cause injuries of periprosthetic osteocytes via activation of apoptosis and autophagy, which promotes osteolysis around the prosthesis osteolysis and joint aseptic loosening.

Effect of oxidative stress on periprosthetic osteolysis induced by TCP wear particles in mouse calvaria and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To explore the effect of oxidative stress on periprosthetic osteolysis induced by TCP wear particles in mouse calvaria and its mechanism.@*METHODS@#Thirty-six male ICR mice were randomly divided into three groups (=12):sham group, TCP wear particles (TCP) group and N-acetyl-L-cysteine (NAC) group. Aperiprosthetic osteolysis model in mouse was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2nd day post-operation, NAC (1.0 mg/kg) was locally injected to the calvarium under the periosteum every other day for 2 weeks. Then, all the mice were sacrificed to obtain blood and the calvaria. Periprosthetic osteolysis in the mouse calvaria was observed by tartrate resistant acid phosphatase (TRAP) staining; serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6); total anti-oxidation capacity (T-AOC) and superoxide dismutase (SOD) activity were examined by ELISA and chemical colorimetry, respectively; protein levels of glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phospho-PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α) and phospho-eIF2α (p-eIF2α) in periprosthetic bone tissue were detected by Western blot.@*RESULTS@#Compared with sham group, serum levels of TNF-α, IL-1β and IL-6, and osteolysis area were increased obviously in TCP group (<0.05), and serum level of T-AOC and SOD activity were decreased significantly in TCP group (<0.05), GRP78 expression, the ratio of p-PERK and PERK, p-eIF2α and eIF2α in the mouse calvaria of TCP group were up-regulated markedly. Compared with TCP group, serum levels of TNF-α, IL-1β and IL-6, and osteolysis area were decreased markedly in NAC group (<0.05), serum level of T-AOC and SOD activity were increased obviously in NAC group (<0.05), and GRP78 expression, the ratio of p-PERK/PERK and p-eIF2α/eIF2α were obviously down-regulated.@*CONCLUSIONS@#Inhibition of oxidative stress can prevent periprosthetic osteolysis induced by TCP wear particles, which may be mediated by inactivation of PERK/eIF2α signaling pathway.

Effect of osteoblast autophagy induced by wear particles on secretion of inflammatory cytokines TNF-α and IL-6 / 医学研究生学报

Objective The relationship between osteoblast autophagy induced by wear particles and secretion of inflammatory cytokines has not been illuminated.The purpose of this study was to investigate the effect of wear particles on the secretion of TNF -α and IL-6 by autophagy of osteoblasts in aseptic loosening. Methods The mouse MC3T3-E1 osteoblasts in logarithmic growth phase were divided into 5 groups:control group(in α-MEM medium),CoCrMo particle group(100 μg/mL CoCrMo particles was added in α-MEM medium),3-MA group(10 mmol/L autophagy inhibitor 3-MA prestimulated osteoblasts in α-MEM medium,3h later 100 μg/mL CoCrMo particles were added),the expression of autophagy marker protein LC-3 in osteoblasts was detected by Western blotting, and the levels of TNF-αand IL-6 were detected by ELISA. Results Compared with the control group,the expression level of auto-phagy marker protein LC-3 was significantly increased in CoCrMo particles group(P<0.05).Compared with CoCrMo particles group,the expression level of LC-3 in 3-MA group was significantly decreased(P<0.05).Compared with control group TNF-α[(0.95± 0.00)pg/mL]and IL-6[(4.67±0.23)pg/mL], CoCrMo particles group TNF-α[(10.35±3.63)pg/mL]and IL-6[(14.27±1.07)pg/mL]secretion level was significantly increased(P<0.05),compared with CoCrMo particles group,the effects of 10 mmol/L 3-MA group to TNF-α[(13.13±5.08)(14.71±5.46)pg/mL]and IL-6[(15.31±0.88),(16.75±3.87)pg/mL]secretion were not significant, while 10 mmol/L 3-MA group TNF-α[The secretion levels of(302.61±45.63)pg/mL]and IL-6[(216.67±27.71)pg/mL]in-creased significantly(P<0.01). Conclusion The osteoblast autophagy induced by CoCrMo particles can inhibit the secretion of in -flammatory cytokines TNF-αand IL-6 in osteoblasts.

Aseptic loosening of artificial joint:old story and advances / 医学研究生学报

Aseptic loosening is the most common chronic complication of total joint arthroplasty,which significantly shortens the life span of prosthesis and leads to mental stress and heavy economic burden of patients.Hence,how to overcome aseptic loosening is a focus in the research of joint arthroplasty.A series of mechanisms participates the pathogenesis of aseptic loosening,including oste-olysis induced by wear particles,micromotion,stress shielding,high fluid pressure,endotoxin and genetic factors.Osteolysis induced by wear particles is the most recognized mechanism.The latest study suggested that autophagy,epigenetic regulation and immunologic derangement all participate the development of osteolysis induced by wear particles.However,the prevention,treatment and even the concept of aseptic loosening is still controverial.We hope that the future study will provide a definite mechanism for aseptic loosening and provide new theoretic evidence for the prevention and treatment of aseptic loosening.

Hot issues related to modern hip prosthetic materials / 医学研究生学报

Artificial prosthetic material is one of the important factors determining the effect of artificial hip replacement.There are mainly three types of interfaces in the prosthetic materials: the fixed in-terface,the friction interface,and the interface between the modular prostheses.Porous metals improve the osseointegration of the bio-logical fixed interface.High crosslinking polyethylene and composite ceramics significantly reduce the wear of the friction interface.The modular prostheses of ceramic ball head can reduce the wear particles and corrosion.However,the prosthesis loosening,wear and metal corrosion are still the most important factors affecting the medium-long term effects of artificial hip replacement.This article reviews the research progress of artificial hip prosthesis materials from the perspective of the three prosthetic interfaces.

The present situati on and prospect of research on artificial joint metal wear particles / 医学研究生学报

The artificial joints containing metal prosthetic components have different degrees of wear particles in the human body,which is the main reason for local osteolysis,inflammatory pseudotumor and prosthesis loosening.The metal wear debris after ar-tificial joint replacement can be derived from the normal wear of the weight-bearing interface volume,or from the edge wear of the non-weight-bearing interface.The particles produced by joint wear are mainly nano-sized particles,and their toxicity is stronger than that of micro-sized particles and ions.The wear particles can cause either local reactions by local accumulation or toxicity symptoms of multiple systems by entering the blood in various forms.Cobalt has the strongest toxicity among various metal particles.Oxidative stress,hyper-sensitivity,endoplasmic reticulum stress,autophagy,and direct destruction are the possible cytotoxic and genotoxic mechanisms,and the corresponding detoxification studies are also related to these mechanisms.There is no definite standard for the increase of the con-centration of metal particles and the clinical symptoms.At present, the main treatment is to remove the prosthesis and symptomatic treatment.Future research will focus on the improvement of prosthetic materials and finding new alternative treatment for joint diseases. Basic research will further explore the mechanism of toxicity of metal particles,especially the discovery of signal pathways and suscepti-bility genes as well as the in vivo and in vitro studies and clinical trials of new antidote.

Effects of Low Intensity Pulsed Ultrasound on Osteocyte Injuries Induced by Tricalcium Phosphate Wear Particles in the Calvaria of Mice / 中国运动医学杂志

Objectives To observe the effect of low intensity pulsed ultrasound (LIPUS) on osteocyte injuries induced by the tricalcium phosphate(TCP) wear particles in the calvaria of mice.Methods Thirty ICR male mice of 6 to 8 weeks were randomly divided into a normal control group(n=10),a model group (n=10) and a LIPUS-treated group(n=10).A murine calvarial model of osteolysis was established in the model and LIPUS-treated groups through injecting TCP particles onto the surface of bilateral parietal bones at week 1,3,5,7 and 11.Mice in the normal group received negative ultrasound probe pressing,while those in the LIPUS-treated received LIPUS radiation.Three months later,the calvarias were obtained.The micro-CT,HE staining,flow cytometry and Western blotting were performed to estimate the calvarial osteolysis,osteocyte death,apoptosis and proteins expression of the dentin matrix protein 1 (DMP-1),sclerosis protein (SOST),glucose-regulated protein78 (GRP78),inositol-requiring enzyme(IRE 1 α),spliced X-box binding protein 1 (XBP1 s),c-Jun N-terminal kinase (JNK) and phosphorylated c-Jun N-terminal kinase(p-JNK) respectively.Results Compared with the normal control group,in the model group the viability of prosthetic osteocytes decreased significantly,and cell apoptosis was more obvious(P＜0.05);the osteocytic marker protein DMP-1 down-regulated significantly,but another marker protein SOST up-regulated significantly,which caused the decline in DMP-1/SOST(P＜0.05).Moreover,the expression levels of GRP78,IRE1,XBPls and p-JNK of the model group increased significantly(P＜0.05) in the calvaria osteocytes compared to the control group.However,in the LIPUS treatment group,osteocyte injuries and endoplasmic reticulum(ER) stress both decreased significantly,shown by a significant increase in the number and activity of osteocytes,DMP-1/SOST,and significant inhibition of the IRE1α-XBP1-JNK activation(P＜0.05).Conclusion LIPUS prevents osteocyte injuries induced by TCP wear particles in the calvaria of mice,which may be due to the inhibition of IRE1α-XBP1-JNK pathway activation through ER stress reaction.

Role of PI3K/Akt Signaling Pathway in the TCP Wear Particles-induced Calvarial Osteolysis in Mice Model / 中国运动医学杂志

Objective To explore the role of the PI3K/Akt signaling pathway in the calvarial osteolysis induced by TCP wear particles in mice model.Methods Thirty-six male ICR mice were randomly divided into a sham group (n=12),TCP group (n=12)and a LY294002-treated group (n=12).A murine calvarial model of osteolysis was established through implanting 30 mg of TCP particles onto the surface of bilateral parietal bones following the removal of the periosteum.On the second postoperative day,LY294002 (5 mg·kg-1)was locally injected to the calvarium under the periosteum three times a week;mice in the sham group received local injection of normal saline (N.S.)in the calvarium,and the injection time was consistent with that of LY294002.Two weeks later,the calvaria and periostea were obtained after the mice were executed.The calvarial osteolysis,bone mineral density (BMD)and bone mineral content(BMC)were analyzed using Micro-CT,Hematoxylin-Eosin (HE)staining was conducted to observe the inflammatrory response and formation of osteoclasts.Real-time PCR was applied to detect the mRNA level of tartrate-resistant acid phosphatase (TRAP),the marker of osteoclasts formation,cathepsin K (CstK),receptor activator for nuclear factor-κB kigand (RANKL)and c-Fos.The release of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6)and IL-1β were measured using enzyme-linked immumsorbent assay (ELISA).Results Micro-CT and histological analysis indicated that LY294002,the specific inhibitor of PI3K,significantly prevented TCP wear particles-induced osteolysis and osteoclastogenesis,and increased BMD and BMC in the calvaria of mice.Real-time PCR data revealed LY294002 significantly suppressed the increase in mRNA level of osteoclastogenic genes such as TRAP,CstK,RANKL and c-Fos in the calvaria of TCP wear particles-implanted group.ELISA assay showed that TCP wear particles-induced release of TNF-α,IL-1β and IL-6 was significantly inhibited by LY294002 treatment.Furthermore,LY294002 significantly attenuated TCP wear particles-triggered activation of Akt,and down-regulated the level of p-AktSer473 and p-AktThr308.Conclusion PI3K/Akt signaling pathway contributes to TCP wear particle-induced osteolysis,and can be developed as a new therapeutic target for the prevention and treatment of bone destruction diseases caused by wear debris.

Research progress on wear particles and periprosthetic osteolysis after artificial joint replacement / 中国骨伤

It is an important influencing factor that the generated wear particles lead to periprosthetic osteolysis after artificial joint replacement. Current research suggests that the primary cause of wear particles results in periprosthetic osteolysis is relate to the prosthetic materials and the stimulations because of these materials generated wear particles to relevant cells such as macrophage, osteoblast, osteoclast. Induced a variety of inflammatory cytokines, activating and openning the cell signal and channels, producing the long term chronic inflammation leads to periprosthetic osteolysis. Therefor, the paper mainly studies the different types of wear particles influence on periprosthetic osteolysis, and the wear particles around the periprosthetic osteolysis mechanism in the process of progress, moreover, to explore how to reduce the occurrence of wear particles and blocking its role in the periprosthetic osteolysis, in order to achieve the purpose of prevention and treatment of periprosthetic osteolysis.

Periprosthetic Mass after Total Hip Replacement / 대한고관절학회지

PURPOSE: To analyze the characteristics and causes of periprosthetic huge mass which occur after treatment by total hip arthroplasty. MATERIALS AND METHODS: Of the patients who had undergone total hip arthroplasty from January 2000 to October 2007, we retrospectively evaluated the 10 patients who suffered huge soft tissue mass. Five of these patients had received metal-on-metal bearing (group 1) prostheses, and the other 5 had received metal-on-polyethylene bearings (group 2). We evaluated the size and location of the mass, the extent of osteolysis, and the hematologic and pathologic examination results. RESULTS: Roentgenographically, the location of the masses varied from the acetabular area to the distal femoral stem. The mean mass diameter of all 10 patients was 14.6 cm(7-21 cm)x6.2 cm(3-9 cm)x7.2 cm(4-12 cm). Osteolytic lesions were found in 3 group 1 patients and 3 patients in group 2. High counts of lymphocytes and eosinophils were present in group 1. High counts of macrophages were present in group 2. CONCLUSION: The occurrence of osteolysis and huge soft mass after total hip arthroplasty is thought to be related to foreign body reaction by polyethylene wear particles and metal hypersensitivity. Outside-in patterned cortical thinning was considered to be indicative of a long standing periprosthetic soft tissue mass effect.

Otinulation of osteolytic cytokine expression by micrometer-diameter wear particles / 基础医学与临床

Objective To evaluate the impact osteolytic cytokines of expression induced by micrometer-diameter wear particles(Ti-6Al-4V and UHMWPE).Methods Filtration air was subcutaneously injected into rats'back 6 times(3 mL q?d).After a week,wear particles suspension(group A: Ti-6Al-4V,group B: UHMWPE) or physiological saline(group C) was injected into air pouch tissues.After 14 days,pouch tissues were obtained from killed rats,and were weighted,wax embedded and stained with hematoxylin and eosin, observed under microscope.AKP of serium with Automated Biochemical Analyzer,IL-6 and TNF-? expression with immunohistochemical method,and mRNA expression of extracellular matrix metalloproteinase inducer(EMMPRIN) with real-time Polymerase Chain Reaction method were detected.Results Air pouch tissues were similar to limiting membrane of periprothesis tissue in the cases of aseptic loosening.As to pouch tissue weight,there was a significant increase in group B than in group C(P

Drug inhibition of wear particles induced osteolysis in rabbits / 中国矫形外科杂志

[Objective]To study the possibility of drug inhibition of wear particle induced osteolysis and aseptic prosthesis loosening in vivo.[Methods]4?8 mm transverse holes were made in femur condyle and tibia plateau of 12 adult rabbits bilaterally.One milligram of CoCr alloy(mean 5.38 ?m),Ti-6Al-4V(mean 3.21 ?m) and UHMWPE(12～200 ?m) particles were implanted into the holes separately.The animals were divided into 4 groups and each group had the same particles combination.Oral drug therapy twice a day was adopted with non-selective COX inhibitor(indomethacin,0.5 mg/kg BW),membrane Ca2+ channel inhibitor(nitrendipine,0.1 mg/kg BW),osteoclast inhibitor(alendronate sodium,0.1mg/kg BW) and blank control(0.9% saline) to the 4 groups separately and randomly according to the double blind principle,which started on the 2nd day postoperatively until 12 weeks at the time of sacrifice.Routine histological observation and calculation of the ratio of bone area(BA) to total tissue area(TTA) were done under the computerized analysis system.[Results]CoCr and Ti alloy particles could seldom be seen in the slices of the groups which showed normal cancellous bone.There were obvious macrophage infiltration and fibroblast proliferation round the particulate UHMWPE in the group of blank controls.It was similar in the groups of indomethacin and nitrendipine though the histological reaction was a little bit weaker and osteotoid tissue could occasionally be seen.UHMWPE particles were totally enclosed in the cancellous bone with little fibrous tissue proliferation in the group of alendronate sodium and the BA/TTA ratio was significantly higher than those at the other groups(P0.05).[Conclusion]This indicates the possibility of inhibition or prevention of osteolysis induced by wear particles by drug therapy especially when alendronate sodium is adopted,and it has significant clinical implications for controlling the most common cause of implant failure.

An in vivo study of the inhibitory effect of erythromycin on wear particles induced osteolysis / 中国矫形外科杂志

[Objective]In present study an in vivo wear particles induced mouse calvarial osteolysis model was used to investigate the inhibitory effect of erythromycin over wear particles induced osteolysis.[Method]Twenty-four male eight-week-old C57BL/J6 mice were allocated into 4 groups: PMMA group receiving 30 mg PMMA particles implantation onto the calvariae,PMMA+2EM group receiving 30 mg PMMA particles implantation and EM 2mg/kg ip injection,PMMA+10EM group receiving 30 mg PMMA particles implantation and EM 10mg/kg ip injection,control group receiving sham operation.Seven days later,mice calvariae were harvested for pathology analysis.[Result]Middle suture area in the control group was 0.079 mm2?0.011 mm2,in PMMA group 0.335 mm2?0.129 mm2.In PMMA+2EM group the area was 0.094 mm2?0.019 mm2,PMMA+10EM group was 0.091 mm2?0.028 mm2.Osteoclasts number in osteolysis area in the control group were 5.3?1.0,in PMMA group 19.2?5.3,PMMA+2EM group was 6.6?1.1,PMMA+10EM group 6.1?1.9.Compared with control group,PMMA particles induced significant osteolysis(P