RESUMEN
Chronic inflammation and extensive osteoclast formation play critical roles in wear-debris-induced peri-implant osteolysis. We investigated the potential impact of dopamine on titanium-particle-induced inflammatory osteolysis in vivo and in vitro. Twenty-eight C57BL/6J mice were randomly assigned to four groups: sham control (PBS treatment), titanium (titanium/PBS treatment), low- (titanium/2 µg kg(-1) day(-1) dopamine) and high-dopamine (titanium/10 µg kg(-1) day(-1) dopamine). After 2 weeks, mouse calvariae were collected for micro-computed tomography (micro-CT) and histomorphometry analysis. Bone-marrow-derived macrophages (BMMs) were isolated to assess osteoclast differentiation. Dopamine significantly reduced titanium-particle-induced osteolysis compared with the titanium group as confirmed by micro-CT and histomorphometric data. Osteoclast numbers were 34.9% and 59.7% (both p < 0.01) lower in the low- and high-dopamine-treatment groups, respectively, than in the titanium group. Additionally, low RANKL, tumor necrosis factor-α, interleukin-1ß and interleukin-6 immunochemistry staining were noted in dopamine-treatment groups. Dopamine markedly inhibited osteoclast formation, osteoclastogenesis-related gene expression and pro-inflammatory cytokine expression in BMMs in a dose-dependent manner. Moreover, the resorption area was decreased with 10(-9) M and 10(-8) M dopamine to 40.0% and 14.5% (both p < 0.01), respectively. Furthermore, the inhibitory effect of dopamine was reversed by the D2-like-receptor antagonist haloperidol but not by the D1-like-receptor antagonist SCH23390. These results suggest that dopamine therapy could be developed into an effective and safe method for osteolysis-related disease caused by chronic inflammation and excessive osteoclast formation.
Asunto(s)
Dopamina/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Osteólisis/inducido químicamente , Osteólisis/tratamiento farmacológico , Titanio/efectos adversos , Animales , Células Cultivadas , Dopamina/administración & dosificación , Inflamación/patología , Interleucina-1beta/análisis , Interleucina-6/análisis , Masculino , Ratones Endogámicos C57BL , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Osteólisis/patología , Ligando RANK/análisis , Receptores de Dopamina D2/metabolismo , Transducción de Señal/efectos de los fármacos , Cráneo/efectos de los fármacos , Cráneo/patología , Factor de Necrosis Tumoral alfa/análisis , Microtomografía por Rayos XRESUMEN
Aseptic loosening is associated with the development of wear debris-induced peri-implant osteolytic bone disease caused by an increased osteoclastic bone resorption and decreased osteoblastic bone formation. However, no effective measures for the prevention and treatment of peri-implant osteolysis currently exist. The aim of this study was to determine whether lithium chloride (LiCl), a selective inhibitor of glycogen synthetase kinase 3 beta (GSK-3ß), mitigates wear debris-induced osteolysis in a murine calvarial model of osteolysis. GSK-3ß is activated by titanium (Ti) particles, and implantation of Ti particles on the calvarial surface in C57BL/6 mice resulted in osteolysis caused by an increase in the number of osteoclasts and a decrease in the number of osteoblasts. Mice implanted with Ti particles were gavage-fed LiCl (50 or 200 mg kg(-1)d(-1)), 6 days per week for 2 weeks. The LiCl treatment significantly inhibited GSK-3ß activity and increased ß-catenin and axin-2 expression in a dose-dependent manner, dramatically mitigating the Ti particle-induced suppression of osteoblast numbers and the expression of bone formation markers. Finally, we demonstrated that inhibition of GSK-3ß suppresses osteoclast differentiation and reduces the severity of Ti particle-induced osteolysis. The results of this study indicate that Ti particle-induced osteolysis is partly dependent on GSK-3ß and, therefore, the canonical Wnt signaling pathway. This suggests that selective inhibitors of GSK-3ß such as LiCl may help prevent and treat wear debris-induced osteolysis.
Asunto(s)
Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Cloruro de Litio/uso terapéutico , Osteólisis/tratamiento farmacológico , Osteólisis/enzimología , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Femenino , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Ratones , Ratones Endogámicos C57BL , Osteólisis/etiología , Osteólisis/patología , Prótesis e Implantes/efectos adversos , Cráneo/efectos de los fármacos , Cráneo/enzimología , Cráneo/patología , Titanio/efectos adversosRESUMEN
OBJECTIVE: The purpose of this study was to present the surgical technique and clinical results of percutaneous compression plate (PCCP) for the treatment of femoral neck fractures. METHODS: Between December 2010 and April 2013, 74 consecutive patients with 74 femoral neck fractures were treated by closed reduction and PCCP implants in our university hospital. Their mean age was 51.3 years (range, 15-83 years); 38 (51.4%) were male and 46 (62.2%) of the fractures were on the left. The patients' clinical and radiographic data were analyzed retrospectively. RESULTS: There were 45 undisplaced (60.8%) and 29 displaced fractures (39.2%). Eight patients (10.8%) were lost to follow-up. The mean duration of follow-up was 18.8 months for the remaining 66 patients. At the last follow-up, mean Harris hip score was 92.9 (range, 75-100), and 65 patients (98.5%) had excellent and good outcomes. Sixty-five patients (98.5%) were able to walk independently and one (1.5%) with walking-sticks. The mean time to clinical fracture healing was 3.9 months. There were no cases of nonunion. Two patients (3.0%) had delayed union and two (3.0%) developed avascular necrosis, one of 29 (3.7%) with a displaced fracture and one of 45 (2.6%) with an undisplaced fracture. There were no other complications or prosthetic replacement. CONCLUSIONS: PCCP is a stable internal fixation device that resists axial and rotational stresses. Our PCCP procedure has a low incidence of nonunion and avascular necrosis.
Asunto(s)
Placas Óseas , Fracturas del Cuello Femoral/cirugía , Fijación Interna de Fracturas/instrumentación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fracturas del Cuello Femoral/diagnóstico por imagen , Estudios de Seguimiento , Fijación Interna de Fracturas/métodos , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Periprosthetic osteolysis and subsequent aseptic loosening are common in implant failure, a complication with revision surgery being the only established treatment. Wear particle-induced inflammation and extensive osteoclastogenesis play critical roles in periprosthetic osteolysis. A recent approach in limiting osteolysis is therefore focused on inhibiting osteoclastic bone resorption. This study aimed to investigate the potential impact of icariin, the major ingredient of Epimedium, on titanium particle-induced osteolysis in a mouse calvarial model. Eighty-four male C57BL/J6 mice were divided randomly into four groups. Mice in the sham group underwent sham surgery only, whereas animals in the vehicle, low- and high-concentration icariin groups received titanium particles. Mice in the low- and high-concentration icariin groups were gavage-fed with icariin at 0.1 or 0.3 mg/g/day, respectively, until sacrifice. Mice in the sham and vehicle groups received phosphate-buffered saline daily. After 2 weeks, mouse calvariae were collected for micro-computed tomography, histomorphometry and molecular analysis. Icariin significantly reduced particle-induced bone resorption compared with the vehicle group. Icariin also prevented an increase in receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio and subsequently suppressed osteoclast formation in titanium particle-charged calvariae. In addition, immunohistochemical analysis and enzyme-linked immunosorbent assay showed icariin significantly reduced expression and secretion of tumor necrosis factor-α, interleukin-1ß and interleukin-6 in the calvariae of titanium-stimulated mice. Collectively, these results suggest that icariin represents a potential treatment for titanium particle-induced osteolysis and could be developed as a new therapeutic candidate for the prevention and treatment of aseptic loosening.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/uso terapéutico , Inflamación/prevención & control , Osteólisis/prevención & control , Cráneo/efectos de los fármacos , Titanio/efectos adversos , Animales , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/aislamiento & purificación , Epimedium/química , Flavonoides/aislamiento & purificación , Inflamación/inducido químicamente , Inflamación/patología , Interleucina-1beta/análisis , Interleucina-6/análisis , Masculino , Ratones , Ratones Endogámicos C57BL , Osteólisis/inducido químicamente , Osteólisis/patología , Cráneo/patología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Wear-particle-induced osteolysis is considered to be the main reason for revision after arthroplasty. Although the exact mechanism remains unclear, inflammatory osteoclastogenesis plays an important role in this process. Strontium ranelate (SR) was found to have a therapeutic effect on osteoporosis in postmenopausal women. Based on prior studies, the present authors hypothesized that SR prevents wear-particle-induced osteolysis through restraining inflammatory osteoclastogenesis. The present study used 80 male C57BL/J6 mice to test this hypothesis in a murine osteolysis model. All experimental animals were randomly divided into four groups: a control group; a SR group; a titanium group; and a titanium+SR group. Once titanium particles had been implanted in mice, the mice were administered SR (900 mg kg(-1) day(-1)) by gavage for 14 days. After 14 days, the calvaria were collected for micro-computed tomography (µCT), histological and molecular analysis. The results of µCT and histomorphometric analysis demonstrated that SR markedly inhibited bone resorption and the generation of tartrate-resistant acid-phosphatase-positive cells in vivo, compared with titanium-stimulated calvaria. Reverse transcription polymerase chain reaction and ELISAs showed that SR stimulated the mRNA and protein expression of osteoprotegerin, and inhibited gene and protein expression of receptor activators of nuclear factor-kappa B ligand in titanium-particle-charged calvaria. In addition, SR obviously reduced the secretion of tumor necrosis factor-α and interleukin-1ß in the calvaria of the titanium group. It was concluded that SR inhibits titanium-induced osteolysis by restraining inflammatory osteoclastogenesis, and that it could be developed as a new drug to prevent and treat aseptic loosening.