RESUMEN
BACKGROUND: Acetabular bone deficiency, especially proximal and lateral deficiency, is a difficult technical problem during primary total hip arthroplasty (THA) in developmental dysplasia of the hip (DDH). We report a new reconstruction method using a medial-reduced cemented socket and additional bulk bone in conjunction with impaction morselized bone grafting (additional bulk bone grafting method). QUESTIONS/PURPOSES: In a population of patients with acetabular dysplasia undergoing THA using a medial-reduced cemented socket and additional bulk bone with impacted morselized bone grafting, we evaluated (1) the radiographic appearance of bone graft; (2) the proportion of cups that developed loosening and subsequent revision; and (3) clinical results (outcome scores and complications). METHODS: Forty percent of 330 THAs for DDH performed at one center between 1999 and 2009 were defined as shallow dysplastic hips. The additional bulk bone grafting method was performed on 102 THAs with shallow acetabulum (31% for DDH) at one center between 1999 and 2009. We used this approach and technique for shallow acetabuli when a cup protruded from the lateral acetabular edge in preoperative templating. The other 132 dysplastic hips without bone grafting had THA performed at the same periods and served as a control. Acetabuli were defined as shallow when the depth was less than or equal to one-fifth of the pelvic height (cranial-caudal length on radiograph). The additional bulk bone grafting technique was as follows: the resected femoral head was sectioned at 1 to 2 cm thickness, and a suitable size of the bulk bone graft was placed on the lateral iliac cortex and fixed by poly-L-lactate absorbable screws. Autologous impaction morselized bone grafting, with or without hydroxyapatite granules, was performed along with the implantation of a medial-reduced cemented socket. We defined an "incorporated" graft as remodeling and trabeculation including rounding off of the protruding edge of a graft beyond the socket. Radiographic criteria used for determining loosening were migration or a continuous radiolucent zone between the prosthesis/bone cement and host bone. Clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) and the Merle d'Aubigne and Postel score; complications were tallied from chart review. The followup was 10 ± 3 years (range, 6-15 years). RESULTS: One acetabular component (1%) with severe shallow and steep acetabuli showed definite radiographic evidence of loosening and was revised. Clinically, the mean JOA score for the hips treated with additional bulk bone grafting THA in this study improved from 39 ± 10 points preoperatively to 95 ± 5 points postoperatively (p < 0.05, paired t-test). The mean Merle d'Aubigne and Postel score for the hips improved from 7 ± 2 points to 17 ± 1 points (p < 0.05, paired t-test). Complications included a Trendelenburg sign in one hip, dislocation in one, and transient partial sciatic nerve palsy in one. Within 3 years 6 months postoperatively, 101 of 102 additional bulk bone grafting cases showed successful bone remodeling and bone graft reorientation without collapse on radiographs. Partial resorption of the additional bone graft on the lateral side was observed in two hips (2%) with socket abduction angles of < 35°. CONCLUSIONS: Achieving stable acetabular fixation is often challenging in the dysplastic hip, especially shallow acetabulum, and a variety of techniques have been described. Early results of combining bulk graft with impaction of morselized graft are promising. Although each surgical technique was well established, further investigation for clinical results of a combination of these techniques might be necessary to confirm longer term outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic study.
Asunto(s)
Acetábulo/cirugía , Cementos para Huesos/uso terapéutico , Trasplante Óseo/métodos , Cabeza Femoral/trasplante , Luxación Congénita de la Cadera/cirugía , Articulación de la Cadera/cirugía , Acetábulo/anomalías , Acetábulo/diagnóstico por imagen , Acetábulo/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/instrumentación , Fenómenos Biomecánicos , Cementos para Huesos/efectos adversos , Remodelación Ósea , Trasplante Óseo/efectos adversos , Estudios de Casos y Controles , Femenino , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/fisiopatología , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/fisiopatología , Articulación de la Cadera/anomalías , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/fisiopatología , Humanos , Prótesis Articulares , Masculino , Persona de Mediana Edad , Oseointegración , Diseño de Prótesis , Falla de Prótesis , Recuperación de la Función , Reoperación , Factores de Tiempo , Tomografía Computarizada por Rayos X , Trasplante Autólogo , Resultado del TratamientoRESUMEN
The linear penetration rates for ceramic femoral heads on conventional and highly cross-linked polyethylene were measured and compared with radiographs taken in the standing and supine position taken three weeks postoperatively and at final follow-up. Seventy-five patients (83 hips) with conventional polyethylene (group-1) and two hundred and seventy five patients (300 hips) with highly cross-linked polyethylene (group-2) were studied. Follow-up periods were 14.5years in group-1 and 8.6years in group-2. The average penetration rates in group-1 were 0.17mm/year in supine position and 0.18mm/year in standing position (P<0.05). On the other hand, the rates in group-2 were 0.03mm/year and 0.04mm/year respectively (P<0.05). Although there were statistical differences between groups, 0.01mm differences are probably not clinically relevant.
Asunto(s)
Artroplastia de Reemplazo de Cadera/instrumentación , Cabeza Femoral/diagnóstico por imagen , Prótesis de Cadera , Falla de Prótesis , Adulto , Anciano , Anciano de 80 o más Años , Materiales Biocompatibles , Cerámica , Femenino , Cabeza Femoral/cirugía , Humanos , Masculino , Persona de Mediana Edad , Polietileno , Postura , Radiografía , Adulto JovenRESUMEN
BACKGROUND: Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D). METHODS: QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0-100). RESULTS: Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5-15, 15-30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group. CONCLUSION: According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.
Asunto(s)
Alprostadil/análogos & derivados , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Etodolaco/uso terapéutico , Dolor de la Región Lumbar/tratamiento farmacológico , Calidad de Vida , Estenosis Espinal/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Actividades Cotidianas , Anciano , Alprostadil/uso terapéutico , Distribución de Chi-Cuadrado , Evaluación de la Discapacidad , Femenino , Humanos , Claudicación Intermitente/tratamiento farmacológico , Vértebras Lumbares , Masculino , Dimensión del Dolor , Estadísticas no Paramétricas , Resultado del Tratamiento , CaminataRESUMEN
BACKGROUND: Broad dissection with a long skin incision and detachment of the gluteus medius muscle performed for rotational acetabular osteotomy (RAO) can result in weakness in abduction strength of the hip. We use a surgical procedure for RAO that minimizes operative invasion of soft tissue and reduces incision length compared with conventional procedures. QUESTIONS/PURPOSES: We evaluated the clinical results of this less-invasive RAO comparing it with the more-invasive prior procedure with respect to improvement in clinical hip scores and radiographic coverage and overall hip survival after the procedure. METHODS: In this less-invasive exposure, the medial gluteus muscle is retracted to expose the ilium without detachment from the iliac crest. Similarly, the rectus femoris muscle tendon is retracted, not excised. The lateral part of the osteotomized ilium is cut to form the bone graft instead of harvesting it from the outer cortical bone of the ilium. Between 2000 and 2009, 62 patients (71 hips) underwent this procedure. Twenty-eight hips had early-stage osteoarthritis and 43 had advanced-stage osteoarthritis. Mean patient age was 40 years at the time of surgery. We evaluated improvement in hip scores (Merle d'Aubigné-Postel, Japanese Orthopaedic Association) and radiographic appearance (lateral center-edge angle, Sharp's angle, acetabular head index [AHI]). Kaplan-Meier survivorship analysis was performed. Mean followup was 5 years (range, 2.0-10.4 years). RESULTS: Clinical hip scores improved postoperatively. On average, lateral center-edge angle, Sharp's angle, and AHI improved by 38°, 11°, and 42%, respectively. Predicted 10-year survival rates were 100% and 72% for hips with early- and advanced-stage osteoarthritis, respectively. CONCLUSIONS: In hips with early-stage osteoarthritis treated by this less-invasive approach, no progression of osteoarthritis was documented and Trendelenburg gait was avoided. However, further investigation is necessary for hips with advanced-stage osteoarthritis. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Asunto(s)
Acetábulo/cirugía , Luxación Congénita de la Cadera/complicaciones , Luxación Congénita de la Cadera/cirugía , Osteoartritis de la Cadera/etiología , Osteoartritis de la Cadera/cirugía , Osteotomía/métodos , Acetábulo/anomalías , Acetábulo/diagnóstico por imagen , Adulto , Anciano , Femenino , Fluoroscopía , Luxación Congénita de la Cadera/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/diagnóstico por imagen , Rotación , Resultado del TratamientoRESUMEN
Fourteen hips in 14 patients (all female; average age, 64 years) with severe bone defects due to developmental dysplasia of the hip or migration of the socket were treated with hydroxyapatite block with impacted morselized bone graft in conjunction with a cemented socket. All patients were followed clinically in a prospective fashion, and radiographs were analyzed retrospectively. One initial patient had 17-year follow-up, whereas the remaining 13 patients had follow-up between 4 and 6.5 years. No acetabular components were revised, including the socket of a 17-year postoperative case that remains rigidly fixed and supported by the graft and hydroxyapatite block with only mild polyethylene wear and minor osteolysis. Osteointegration and good clinical outcome were achieved in all cases by reconstruction with this technique in total hip arthroplasty.
Asunto(s)
Acetábulo/anomalías , Artroplastia de Reemplazo de Cadera/métodos , Cementos para Huesos , Trasplante Óseo/métodos , Durapatita , Luxación Congénita de la Cadera/cirugía , Prótesis de Cadera , Acetábulo/cirugía , Anciano , Artroplastia de Reemplazo de Cadera/instrumentación , Femenino , Estudios de Seguimiento , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/cirugía , Humanos , Incidencia , Persona de Mediana Edad , Osteólisis/epidemiología , Polietileno , Estudios Prospectivos , Radiografía , Reoperación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: In degenerative lumbar spinal disease with nerve root compression, the L5 and S1 nerve roots are the most often affected and the L3 nerve root is involved infrequently. The purpose of this study was to investigate the characteristics of L3 nerve root radiculopathy. METHODS: Seventeen consecutive patients with L3 radiculopathy were treated. The symptomatic nerve roots were determined by the pain distribution, the neurologic findings, and selective nerve root injection. The clinical characteristics and outcomes of these patients were assessed retrospectively. RESULTS: The average age was 76 years. The spinal diseases that were associated with L3 radiculopathy were lumbar canal stenosis in 6 patients, lumbar extraforaminal stenosis and lumbar disk herniation in 5 each, and lumbar canal stenosis with degenerative scoliosis in 1. The patients' symptoms were thigh pain in 12 patients, and hip or knee pain in 5. Four patients were nonambulatory because of severe pain. Although a sensory disturbance was reported in 9 patients, motor weakness was present in 2. Selective nerve root injection was completely effective in 10 patients. Six had decompressive surgery and/or fusion followed by a favorable outcome. Four patients were misdiagnosed and received conservative treatment for hip and/or knee joint diseases. CONCLUSIONS: L3 radiculopathy was characterized by various lower limb pain and neurologic deficit. Selective nerve root injection was effective for most patients. In elderly patients who do not respond to treatment for hip and/or knee joint diseases, L3 nerve root radiculopathy should be considered as the cause of lower limb pain.
Asunto(s)
Vértebras Lumbares/patología , Manejo del Dolor , Dolor/etiología , Radiculopatía/etiología , Radiculopatía/terapia , Raíces Nerviosas Espinales/patología , Anciano , Anciano de 80 o más Años , Anestésicos Locales/uso terapéutico , Antiinflamatorios/uso terapéutico , Descompresión Quirúrgica/métodos , Descompresión Quirúrgica/estadística & datos numéricos , Discectomía/métodos , Discectomía/estadística & datos numéricos , Femenino , Humanos , Inyecciones Intralesiones/métodos , Inyecciones Intralesiones/estadística & datos numéricos , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/patología , Desplazamiento del Disco Intervertebral/cirugía , Lidocaína/uso terapéutico , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Debilidad Muscular/etiología , Debilidad Muscular/terapia , Dolor/fisiopatología , Radiculopatía/fisiopatología , Radiografía , Estudios Retrospectivos , Fusión Vertebral/métodos , Fusión Vertebral/estadística & datos numéricos , Raíces Nerviosas Espinales/fisiopatología , Estenosis Espinal/complicaciones , Estenosis Espinal/patología , Estenosis Espinal/cirugía , Esteroides/uso terapéutico , Resultado del TratamientoRESUMEN
This study was designed to investigate effects of heat on the bone-inducing activity of recombinant human bone morphogenetic protein (rhBMP)-2. rhBMP-2 samples were heated at 50, 70, 90, or 100 degrees C for 15 min, or 1, 2, 4, or 8 h, or autoclaved at 120 degrees C for 15 min. The bone-inducing activity of the rhBMP-2 before and after heating was assayed in in vivo and in vitro systems. For the in vivo assay, 5 microg rhBMP-2 samples were impregnated into porous collagen disks (6 mm in diameter, 1 mm thickness), freeze dried, and implanted into the back muscles of ddY mice. Three weeks later, the implant was harvested from the host and examined for ectopic new bone tissue by radiography. The new bone mass was quantified by single-energy X-ray absorptiometry. The in vitro activity of the rhBMP-2 was assayed by adding the BMP sample at a concentration of 100 ng/ml to cultures of MC3T3-E1 cells. After 48 h, the alkaline phosphatase activity was measured. After heating at 50 degrees or 70 degrees C, no significant reduction in bone-inducing activity was noted in either in vivo or in vitro assay systems unless the protein was exposed to sustained heat at 70 degrees C for 8 h, based on in vitro assay data. However, heating above 90 degrees C and for longer periods led to a decrease in the biological activity of the rhBMP-2 in a time- and temperature-dependent manner. rhBMP-2 was rendered inactive when exposed to temperatures at or in excess of 120 degrees C.
Asunto(s)
Proteínas Morfogenéticas Óseas/farmacología , Calor , Factor de Crecimiento Transformador beta/farmacología , Fosfatasa Alcalina/biosíntesis , Animales , Proteína Morfogenética Ósea 2 , Proteínas Morfogenéticas Óseas/aislamiento & purificación , Calcificación Fisiológica , Línea Celular , Electroforesis en Gel de Poliacrilamida , Inducción Enzimática/efectos de los fármacos , Humanos , Ratones , Proteínas Recombinantes/farmacología , Factor de Crecimiento Transformador beta/aislamiento & purificaciónRESUMEN
We investigated the enhancement of new bone |formation elicited ectopically by recombinant human bone morphogenetic protein-2 (rhBMP-2), using parathyroid hormone (PTH) and a phosphodiesterase inhibitor (PDEi), pentoxifylline (PTX), in an animal model. Collagen sponge sheet discs containing rhBMP were implanted onto the back muscles of mice. PTX alone (200 mg/kg body weight [BW]), PTH(1-34) (10 microg/kg BW), PTX plus PTH (200 mg/kg BW and 10 microg/kg BW, respectively), or vehicle (control) were injected subcutaneously daily for 3 weeks after implantation. At the end of this period, rhBMP-2-induced ectopic ossicles were harvested from each group of animals. Ossicles from the PTX-treated group were significantly larger in size, with unchanged bone mineral density (BMD), as compared with the ossicles from the controls. In contrast, the ossicles from the PTH-treated group had significantly higher BMD, but showed no difference in size when compared with those from the control animals. The ossicles of the PTX + PTH treatment group were significantly larger than those of the control and PTH treatment groups. In addition, the BMD of the harvested tissues from the PTX + PTH treatment group was signifi-cantly higher than that of tissues from the control and PTX treatment groups. Although the calcium content of ossicles was significantly higher in the PTX-, PTH-, and PTX + PTH-treated groups than in the control group, the Ca content of ossicles from the PTH + PTX-treated group was highest (two times that of controls), followed by the PTH- and PTX-treated groups.
Asunto(s)
Proteínas Morfogenéticas Óseas/farmacología , Huesos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Hormona Paratiroidea/farmacología , Pentoxifilina/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Factor de Crecimiento Transformador beta , Animales , Densidad Ósea/efectos de los fármacos , Proteína Morfogenética Ósea 2 , Huesos/diagnóstico por imagen , Huesos/patología , Calcio/análisis , Osículos del Oído/metabolismo , Humanos , Masculino , Ratones , Radiografía , Proteínas Recombinantes/farmacologíaRESUMEN
The purpose of our study was to assess microinvasion in a case of synovial sarcoma by means of the reverse transcriptase polymerase chain reaction (RT-PCR) for detecting SYT-SSX fusion transcripts. Furthermore, we tried to compare the RT-PCR results with those obtained by conventional histopathological examination. A 45-year-old man with synovial sarcoma in the left lower leg underwent above-knee amputation and partial resection of the right lung because of local recurrence and metastasis to the lung. We obtained samples from the tumor and from locations at distances of 1, 3, and 5 cm from the tumor margin in the amputated limb. Samples were also obtained from the resected pulmonary tumor and peripheral blood. SYT-SSX1 chimeric genes could be detected in the samples obtained from up to 3 cm outside the tumor by RT-PCR. Histopathological examination confirmed tumor cells up to 1 cm from the tumor margin. We believe that using a molecular assay in addition to a histopathological examination provides a more sensitive and accurate assessment of the surgical margin.
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Proteínas de Fusión Oncogénica/genética , Sarcoma Sinovial/patología , Neoplasias Cutáneas/patología , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sarcoma Sinovial/genética , Neoplasias Cutáneas/genéticaRESUMEN
UNLABELLED: The mechanism of ectopic bone formation has not been clear. After BMP-2 implantation into the back muscles of 198 mice, expression of BMPR-1A, -2, and Noggin was increased during the early phase of the reaction. The results suggest that positive and negative feedback mechanisms modulate ectopic osteogenesis induced by this growth factor. INTRODUCTION: The expression of bone morphogenetic protein receptors (BMPRs) and Noggin during ectopic bone formation after implantation of BMP-2 into the back muscles of adult mice was investigated in this study. METHODS: One hundred ninety-eight male ddy mice were divided into groups and received either collagen disks containing BMP-2, collagen disks alone, or sham surgery with no disk implantation. Changes in the temporal and spatial expression profiles of BMPRs and Noggin were examined by Northern blotting, in situ hybridization, Western blotting, and immunohistochemistry. RESULTS AND CONCLUSIONS: In the BMP group, expression of BMPR-1A, -2, and Noggin mRNA and protein was enhanced 2-4 days after implantation in undifferentiated mesenchymal cells and regenerating muscle fibers located close to the BMP-retaining implants. On day 7, the expression was also observed in cartilage cells, and after day 14, in the osteoblastic cells around bone tissue. The level of expression peaked at day 4 after implantation and persisted at a much lower level during the bone forming process. No significant expression of BMPR-1B was detected at the mRNA and protein levels during the bone-forming reaction. In the BMP free control groups, a mild enhancement of BMPR-2 expression was also noted around the implant, but this was not observed for BMPR-1A, -1B, or Noggin. Upregulated expression of BMPR-1A, -2, and Noggin in undifferentiated mesenchymal cells and regenerating muscle fibers occurs during the early phase of BMP-2-induced bone formation. The coordinate expression of these positive and negative regulators of BMP signaling points to a potential regulatory mechanism for bone induction.
Asunto(s)
Proteínas Morfogenéticas Óseas/biosíntesis , Proteínas Morfogenéticas Óseas/metabolismo , Huesos/metabolismo , Biosíntesis de Proteínas , Proteínas Serina-Treonina Quinasas/biosíntesis , Proteínas , Receptores de Factores de Crecimiento/biosíntesis , Factor de Crecimiento Transformador beta , Animales , Northern Blotting , Western Blotting , Proteína Morfogenética Ósea 2 , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1 , Proteínas Portadoras , Diferenciación Celular , Colágeno/metabolismo , Retroalimentación Fisiológica , Regulación de la Expresión Génica , Inmunohistoquímica , Hibridación in Situ , Masculino , Ratones , Músculos/metabolismo , Músculos/patología , Osteogénesis , ARN/metabolismo , Factores de TiempoRESUMEN
PURPOSE: To determine the healing potential of fibrillated cartilage in osteoarthritic (OA) knees when the mechanical condition is corrected. TYPE OF STUDY: Prospective study. METHODS: Subjects were patients treated with high tibial osteotomy alone for medial-compartment OA knees. They were divided into 2 groups on the basis of the Outerbridge classification; group A consisted of 37 grade IV knees (eburnation group), and group B consisted of 36 grade III knees (fibrillation group). Twelve months after surgery, the repair of joint cartilage was evaluated for arthroscopic finding and histology. RESULTS: Arthroscopic examination of the femoral joint surface showed that, in group A, 9 knees (24%) were grade II, 14 (38%) were grade III, and 14 (38%) were grade IV; in group B, 3 knees (9%) were grade II, 30 (91%) were grade III, and none were grade IV. On the other hand, examination of the tibial joint surface showed that, in group A, 5 knees (16%) were grade II, 15 (47%) were grade III, and 12 (37%) were grade IV; in group B, 3 knees (9%) were grade II, 28 (80%) were grade III, and 5 (11%) were grade IV. Thus, the incidence of cartilage repair was significantly higher in group A than in group B on both femoral (P <.01) and tibial (P <.05) joint surface. Histologic findings showed most of the nonrepaired joint surface of fibrillated cartilage appeared to be hyaline cartilage, but repair tissues of eburnated bone were mainly fibrocartilage. CONCLUSIONS: The repair of fibrillated cartilage was not promoted, but its degeneration was prevented by correction of the mechanical status. Our results show that fibrillated cartilage in OA knees has little potential for repair even though the mechanical status is corrected.
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Cartílago Articular/patología , Osteoartritis de la Rodilla/cirugía , Tibia/cirugía , Cicatrización de Heridas , Anciano , Artroscopía , Femenino , Fémur/patología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/patología , Osteotomía , Tibia/patología , Resultado del TratamientoRESUMEN
The cyclic monophosphate nucleotides (cyclic adenosine monophosphate [cAMP] and cyclic guanosine monophosphate [cGMP]) are found ubiquitously in mammalian cells and act as second messenger transducers to effect the intracellular actions of a variety of hormones, cytokines, and neurotransmitters. In turn, these nucleotides also modulate the signal transduction processes regulated by a range of cytokines and growth factors. Previously, we have reported that pentoxifylline, a nonselective phosphodiesterase (PDE) inhibitor, can promote osteoblastic differentiation by elevating intracellular cAMP levels and, consequently, enhance bone formation in vivo and in vitro. In this study, reverse-transcription polymerase chain reaction (RT-PCR) analysis of the osteoblastic cell lines, MC3T3-E1 and ST2 revealed the presence of PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, and PDE9. We examined the effect of selective inhibitors for a respective PDE isozyme on the capacity of bone morphogenetic protein 4 (BMP-4)-induced alkaline phosphatase (ALP) activity, a cellular differentiation marker, in cells with osteogenetic potential. The results indicate that selective inhibitors for PDE2, PDE3, and PDE4 enhanced the BMP-4-induced ALP activity in a dose-dependent manner in ST2 cells but not in MC3T3-E1 cells. Northern blot analysis also revealed that the selective inhibitors for PDE2, PDE3, and PDE4 enhanced the levels of expression of messenger RNAs (mRNAs) of ALP, osteopontin (OP), and collagen type I in ST2 cells but not in MC3T3-E1 cells except for the treatment with PDE4 inhibitor. Given these data, we conclude that PDE isozymes are involved in the modulation of osteoblastic differentiation mainly at an early stage. Additionally, selective inhibitors for PDE2, PDE3, and PDE4 appear to promote the differentiation of osteogenic precursor cells toward an osteoblastic phenotype.
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Diferenciación Celular , Osteoblastos/enzimología , Hidrolasas Diéster Fosfóricas/metabolismo , Fosfatasa Alcalina/efectos de los fármacos , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Proteína Morfogenética Ósea 4 , Proteínas Morfogenéticas Óseas/metabolismo , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Isoenzimas , Ratones , Milrinona/farmacología , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteopontina , Inhibidores de Fosfodiesterasa/farmacología , Hidrolasas Diéster Fosfóricas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rolipram/farmacología , Sialoglicoproteínas/efectos de los fármacos , Sialoglicoproteínas/genéticaRESUMEN
Bone morphogenetic protein (BMP) is a bone-derived growth factor capable of promoting the differentiation of mesenchymal cells into osteogenic lineage pathways. Recently, immunosuppressants were reported to cause a moderate increase in osteoblastic differentiation in a rat osteoblast-like osteosarcoma cell line. If immunosuppressants can induce osteoblastic differentiation, it will be useful for bone tissue transplantation. We assessed the effect of immunosuppressants with or without BMP-4 on inducing osteoblastic differentiation in osteoblast-like and other mesenchymal cells. FK506, an immunosuppressant often used clinically, induced a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, one of the markers of osteoblast differentiation, in cells derived from mesenchyma. In the presence of BMP-4, ALP activity, mRNA levels of ALP and osteocalcin increased. FK506 was found to not only stimulate osteoblastic differentiation, but also to enhance BMP-4 induced osteoblastic differentiation. These results suggest that FK506 promotes differentiation of osteoblastic cells.