阿仑磷酸钠和辛伐他汀对体外培养成骨细胞的影响

目的探讨辛伐他汀和阿仑磷酸钠对体外培养成骨细胞的影响。方法分离3周龄成骨细胞，体外培养时以辛伐他汀和阿仑磷酸钠刺激，观察成骨细胞碱性磷酸酶水平和成骨细胞增殖率。结果辛伐他汀、阿仑磷酸钠可以促进成骨细胞增殖，增加碱性磷酸酶的分泌，二者共同作用后作用更显著。结论辛伐他汀和阿仑磷酸钠能促进成骨细胞增殖和分泌碱性磷酸酶，可以联合作用促进骨形成。     

人骨肉瘤的超微结构研究

通过6例人骨肉瘤的病理学和超微结构研究,在电镜下将骨肉瘤细胞分类为骨母细胞、软骨母细胞、纤维母细胞、原始间叶细胞和多核巨细胞等五型。各型瘤细胞的组织发生均来源于多能性原始间叶细胞。瘤细胞的恶性特点,除具有肿瘤细胞共同的形态特征之外,核内常见管状包涵体,胞质里有散在的致密颗粒和无定向排列的微丝,间质胶原纤维中沉积着羟基磷灰石结晶颗粒。     

Calcitonin has direct effects on3[H]-thymidine incorporation and alkaline phosphatase activity in human osteoblast-line cells

Summary Calcitonin had direct and dose-dependent actions on human osteoblast-line cells (in serum-free monolayer culture) to increase cell proliferation and alkaline phosphatase activity/mg cell protein. Salmon calcitonin increased (human osteosarcoma) SaOS-2 cell proliferation, as evidenced by dose-dependent increases in³[H]-thymidine incorporation into DNA (e.g., 153% of control after 20 h exposure at 0.1 nM,P<0.01), and MTT (thyzolyl blue) reduction/deposition (e.g., 161% of control after 72 h exposure at 0.03 nM). Continuous exposure was not required to elicit these proliferative responses. These effects were not unique to salmon calcitonin or to SaOS-2 cells. Similar effects were seen with human calcitonin (but not heat-inactivated human calcitonin) and with (human osteosarcoma) TE-85 cells and human osteoblast-line cells prepared from femoral heads. In addition to effects on cell proliferation, calcitonin also increased alkaline phosphatase-specific activity in SaOS-2 cells (e.g., 180% of control after 72 h of exposure to 0.1 nM salmon calcitonin,P<.005).     

Integrins,insulin like growth factors,and the skeletal response to load

Bone loss during skeletal unloading, whether due to neurotrauma resulting in paralysis or prolonged immobilization due to a variety of medical illnesses, accelerates bone loss. In this review the evidence that skeletal unloading leads to bone loss, at least in part, due to disrupted insulin like growth factor (IGF) signaling, resulting in reduced osteoblast proliferation and differentiation, will be examined. The mechanism underlying this disruption in IGF signaling appears to involve integrins, the expression of which is reduced during skeletal unloading. Integrins play an important, albeit not well defined, role in facilitating signaling not only by IGF but also by other growth factors. However, the interaction between selected integrins such as αυβ3 and β1 integrins and the IGF receptor are of especial importance with respect to the ability of bone to respond to mechanical load. Disruption of this interaction blocks IGF signaling and results in bone loss. The skeletal response to mechanical load is critical for maintenance of skeletal integrity. This review will assess the interacting roles that insulin like growth factor I (IGF-I) signaling and selected integrins play in this response. Skeletal unloading results in decreased integrin expression, resistance to the anabolic actions of IGF-I, and bone loss.     

Parathyroid hormone stimulates phosphoinositide metabolism and intracellular calcium mobilization in osteoblast-like clone MC3T3-E1 cells

The effects of parathyroid hormone (rat 1–34 fragment, rPTH) on phosphoinositide metabolism and intracellular Ca²⁺ mobilization were studied in a osteoblast-like clone MC3T3-E1 cells. rPTH caused a transient rise in intracellular Ca²⁺ in a dose-dependent manner. Significant Ca²⁺ increase was still observed under the extracellular Ca²⁺-free condition. In addition, 100nM rPTH stimulated rapid formation of both 1,2-diacylglycerol (1,2-DAG) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P₃), indicating agonist-triggered hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP₂). The current observations suggested that the rPTH-induced increase of intracellular Ca²⁺ was in part due to internal Ca²⁺ release mediated by Ins(1,4,5)P₃. These results indicate possible involvement of phosphoiniositide metabolism in signal transduction of PTH-stimulated osteoblastic cells.     

Expression of bone sialoprotein (BSP) in developing human tissues

Summary Bone sialoprotein (BSP) and its messenger RNA were localized in developing human skeletal and nonskeletal tissues by means of immunohistochemistry andin situ hybridization. Both protein and mRNA were found in mature, bone-forming cells but not in their immature precursors. In addition, osteoclasts displayed positive immunostaining and high densities of autoradiographic grains byin situ hybridization experiments. BSP was expressed in fetal epiphyseal cartilage cells, particularly in hypertrophic chondrocytes of growth plates. Though neither the protein nor the mRNA were identified in a variety of other connective and nonconnective tissues, an unexpected finding was the expression of BSP in the trophoblast cells of placenta. These findings show that BSP is primarily an osteoblast-derived component of the bone matrix expressed at late stages of differentiation. We have also found that osteoclasts produce BSP, possibly as a mediator of cell attachment to bone.     

Bone Histomorphometry in Male Idiopathic Osteoporosis

The pathogenesis of male osteoporosis at the cellular level is still elusive. We performed histomorphometric analysis of bone biopsy samples from 51 eugonadal men with idiopathic osteoporosis. Their median age was 54 (range 29–73) years. Eighty-two percent of the patients had a fracture history, and 57% had vertebral fractures. Bone volume, trabecular thickness, wall thickness, and osteoid thickness were significantly reduced in osteoporotic men compared with healthy men. Erosion depth was similar, as were the bone remodeling parameters such as bone formation rate, mineral apposition rate, and activation frequency. In the osteoporotic men, osteoid thickness was correlated to bone mineral density at the lumbar spine (R ² = 0.19, P < 0.01); together with wall thickness, the two parameters could explain 27% of the variation in lumbar spine bone mineral density. The osteoid thickness was correlated to anthropometric variables such as body weight (R ² = 0.24, P < 0.001) and body mass index (R ² = 0.14, P < 0.01), as well as to serum estradiol levels (R ² = 0.14, P < 0.01) and to the ratio insulin-like growth factor-1 (IGF-1) to IGF-binding protein-1 (IGFBP-1) (R ² = 0.12, P < 0.01). Regression analysis showed that 36% of the variation in osteoid thickness could be predicted by body weight and estradiol levels. In conclusion, bone histomorphometry in male idiopathic osteoporosis was characterized by thin bone structural units, which might suggest osteoblast dysfunction. Bone histomorphometry parameters were associated with low body weight, low estradiol levels, and increased levels of IGFBP-1, supporting the notion that estrogens and IGFs play regulatory roles in male bone turnover.     

Bisphosphonate Treatment Increases the Size of the Mandibular Condyle and Normalizes Growth of the Mandibular Ramus in Osteoprotegerin-Deficient Mice

Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor receptor family which plays a crucial role in negative regulation of osteoclastic bone resorption. OPG-deficient (OPG–/–) mice develop severe osteoporosis caused by significant enhancement of bone resorption by osteoclasts. We investigated the effect of administering bisphosphonate on mandibular growth and development in OPG–/– mice. Eight-week-old male OPG–/– mice and wild-type (WT) mice were administered bisphosphonate (1.25 mg/kg body weight) intraperitoneally once every 3 days for 30 days. All bone formation-related parameters and bone resorption-related parameters were significantly lower in OPG–/– mice with bisphosphonate than in those without bisphosphonate. The volume of the whole condyle and the mandibular length in OPG–/– mice without bisphosphonate were significantly smaller than in WT mice without bisphosphonate. Bisphosphonate treatment of the OPG–/– mice resulted in an increase in the volume of the mandibular condyle and mandibular ramus length. In fact, the mandibular ramus length in OPG–/– mice with bisphosphonate was similar to the length in WT mice without bisphosphonate. Histologically, the surface irregularity of the mandibular condyle that was observed in the OPG–/– mice without bisphosphonate tended to be less marked in the OPG–/– mice with bisphosphonate, and the proportion of the area of the cartilage layer relative to the whole condyle was significantly larger in OPG–/– mice with bisphosphonate than in those without bisphosphonate. In conclusion, bisphosphonate treatment results in an increase in mandibular condylar dimensions and normalization of mandibular ramus growth.