ABSTRACT
OBJECTIVE@#To investigate the expression of pyruvate kinase M2 (PKM2) in bone marrow mesenchymal stem cells (BMSCs) in myeloma bone disease (MBD) and its effect on osteogenic and adipogenic differentiation of BMSCs.@*METHODS@#BMSCs were isolated from bone marrow of five patients with multiple myeloma (MM) (MM group) and five with iron deficiency anemia (control group) for culture and identification. The expression of PKM2 protein were compared between the two groups. The differences between osteogenic and adipogenic differentiation of BMSCs were assessed by using alkaline phosphatase (ALP) and oil red O staining, and detecting marker genes of osteogenesis and adipogenesis. The effect of MM cell line (RPMI-8226) and BMSCs co-culture on the expression of PKM2 was explored. Functional analysis was performed to investigate the correlations of PKM2 expression of MM-derived BMSCs with osteogenic and adipogenic differentiation by employing PKM2 activator and inhibitor. The role of orlistat was explored in regulating PKM2 expression, osteogenic and adipogenic differentiation of MM-derived BMSCs.@*RESULTS@#Compared with control, MM-originated BMSCs possessed the ability of increased adipogenic and decreased osteogenic differentiation, and higher level of PKM2 protein. Co-culture of MM cells with BMSCs markedly up-regulated the expression of PKM2 of BMSCs. Up-regulation of PKM2 expression could promote adipogenic differentiation and inhibit osteogenic differentiation of MM-derived BMSCs, while down-regulation of PKM2 showed opposite effect. Orlistat significantly promoted osteogenic differentiation in MM-derived BMSCs via inhibiting the expression of PKM2.@*CONCLUSION@#The overexpression of PKM2 can induce the inhibition of osteogenic differentiation of BMSCs in MBD. Orlistat can promote the osteogenic differentiation of BMSCs via inhibiting the expression of PKM2, indicating a potential novel agent of anti-MBD therapy.
Subject(s)
Humans , Adipogenesis , Bone Diseases/metabolism , Bone Marrow Cells , Cell Differentiation , Cells, Cultured , Mesenchymal Stem Cells/physiology , Multiple Myeloma/metabolism , Orlistat/pharmacology , Osteogenesis/geneticsABSTRACT
Abstract Bone development and healing processes involve a complex cascade of biological events requiring well-orchestrated synergism with bone cells, growth factors, and other trophic signaling molecules and cellular structures. Beyond health processes, MMPs play several key roles in the installation of heart and blood vessel related diseases and cancer, ranging from accelerating metastatic cells to ectopic vascular mineralization by smooth muscle cells in complementary manner. The tissue inhibitors of MMPs (TIMPs) have an important role in controlling proteolysis. Paired with the post-transcriptional efficiency of specific miRNAs, they modulate MMP performance. If druggable, these molecules are suggested to be a platform for development of "smart" medications and further clinical trials. Thus, considering the pleiotropic effect of MMPs on mammals, the purpose of this review is to update the role of those multifaceted proteases in mineralized tissues in health, such as bone, and pathophysiological disorders, such as ectopic vascular calcification and cancer.
Subject(s)
Humans , Bone Remodeling/physiology , Matrix Metalloproteinases/physiology , Extracellular Matrix/physiology , Osteoblasts/physiology , Bone Diseases/physiopathology , Bone Diseases/metabolism , Disease Progression , Tissue Inhibitor of Metalloproteinases/physiology , Vascular Calcification/physiopathology , Vascular Calcification/metabolism , Matrix Metalloproteinase Inhibitors/therapeutic use , Neoplasms/physiopathology , Neoplasms/metabolismABSTRACT
Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis.
Subject(s)
Bone Diseases/etiology , Bone Diseases/metabolism , Bone Diseases/pathology , Humans , Thyrotoxicosis/complications , Thyrotoxicosis/metabolism , Thyrotoxicosis/pathologyABSTRACT
A redução dos níveis de vitamina D e a retenção de fósforo na doença renal crônica estimulam a proliferação celular da paratireóide, enquanto a liberaçãoaguda de PTH pela glândula é mais dependente do nível de cálcio ionizado no líquido extracelular. Os balanços de fósforo e de cálcio nos pacientes emdiálise assim como a influência que exercem sobre a função da paratireóide e a remodelação óssea são modificáveis por alguns medicamentos como osquelantes de fósforo e a vitamina D e, também, pela prescrição da diálise. Em especial, a concentração de cálcio no dialisato, tanto na hemodiálise quantona diálise peritoneal, pode ter um papel importante no manuseio do hiperparatireoidismo secundário.
Low vitamin D levels and phosphorus retention stimulate parathyroid cell proliferation in chronic kidney disease, whereas acute glandular PTH release is mainly dependent on ionized calcium concentration in the extracellular fluid. Phosphorus and calcium balance in patients on dialysis and their effects on parathyroid function and bone turnover can be influenced by medications such as phosphate binders and vitamin D as well as by dialysis prescription. Of note, the calcium concentration in dialysis solution, on either hemodialysis or peritoneal dialysis can have a special role in the management of renal osteodystrophy.
Subject(s)
Humans , Peritoneal Dialysis/adverse effects , Peritoneal Dialysis , Renal Dialysis/adverse effects , Renal Dialysis , Bone Diseases/complications , Bone Diseases/metabolism , Phosphorus/administration & dosageABSTRACT
É apresentada revisão de literatura envolvendo origem embrionária e histofisiologia do tecido ósseo, bem como as principais modificações fisiopatológicas sofridas por este tecido nas principais doenças metabólicas.
Subject(s)
Humans , Bone and Bones , Bone Diseases , Bone and Bones/embryology , Bone and Bones/metabolism , Bone Diseases/metabolism , Bone and Bones/physiologyABSTRACT
Objetivo. Determinar en la tercera vértebra lumbar de un grupo de hombres y mujeres de la Ciudad de México la densidad ósea estableciendo y correlacionando las características morfométricas del cuerpo vertebral, por medio de técnicas específicas y por detectar grupos con alteraciones de osteoporosis y osteopenia. Metodología. El estudio se realizó en la tercera vértebra lumbar de 23 cadáveres del Servicio Médico Forense, 8 mujeres de 31 a 72 años y 15 hombres de 25 a 62 años. Los estudios efectuados fueron: radiológicos, densitometría ósea y análisis de imagen, en la que se determinó espesor de las trabéculas verticales y horizontales. Con microscopia electrónica de barrido por medio de la Técnica de rayos X se determinó en forma semicuantitativa la presencia de calcio, fósforo, magnesio y sodio y en forma cualitativa la distribución de calcio en una área determinada del cuerpo vertebral mediante la técnica de energía dispersada de rayos X. Resultados. Estudio radiológico en el grupo de mujeres ninguna vértebra estudiada fue normal, todas ellas presentaron cambios degenerativos, de éstas cinco con trabeculación aumentada y tres con evidencia de fractura, con respecto al grupo de hombres siete fueron normales y ocho casos con cambios degenerativos de éstos seis presentaron densidad ósea con densitometría con DEXA en el grupo de mujeres sólo una se determinó normal, tres osteopenia y cinco con osteoporosis, en el grupo de varones cinco fueron normales, cinco con osteopenia y cinco con osteoporosis. En la determinación del mapeo de calcio por medio del microscopio de barrido, se pudo observar la distribución de calcio, en los casos normales se observó su distribución se presenta menos densa existiendo áreas en las que el calcio se encuentra disminuido o bien se encuentra ausente. En el estudio morfométrico se determinó el espesor trabecular de nueve vértebras, de cinco mujreses y cuatro hombres, en el grupo de mujeres, una presentó un espesor trabecular promedio normal de 222.1µm, en las cuatro restantes con osteoporosis el rango fue de 126.3 a 156.2 µm, en el grupò de varones se encontraron dos normales con un espesor trabecular promedio de 249.7 µm...