巴戟天甲基异茜草素对破骨细胞性骨吸收的影响

目的研究甲基异茜草素抑制骨吸收的细胞学机制。方法采用原代培养的成骨细胞和骨髓单核细胞联合培养的方法,在1,25-（OH）2VitaminD3和地塞米松作用下,使骨髓单核细胞分化形成破骨细胞。磷酸苯二钠法测定破骨细胞抗酒石酸酸性磷酸酶（Tartrate-resistant acid phosphatase,TRAP）的活性;计算机图像分析技术测定骨片上破骨细胞性骨吸收陷窝的面积;荧光酶标方法测定组织蛋白酶K的活性。结果甲基异茜草素在0.1～10μmol·L^-1范围内,浓度依赖性地抑制破骨细胞形成、分化、TRAP酶活性和在骨片上形成的吸收陷窝的数目和面积。结论甲基异茜草素通过抑制破骨细胞的形成、分化和骨吸收功能来减少骨质的丢失。     

运动性骨疲劳的模拟实验研究

目的 :探讨运动性骨疲劳发生发展的机理。方法 :实验雄性成年兔 2 5只 ,运用高电压、低电流动物刺激仪 ,刺激实验兔进行主动跑跳训练 ,成功地模拟出运动性骨疲劳的动物模型。结果 :2周训练后 ,X线及核素骨显像均呈阴性 ,血甲状旁腺素 (PTH)和血骨钙素 (BGP)显著高于正常组 ,血睾酮 (T)显著低于正常组 ,胫骨皮质骨吸收腔显著增加 ,组织学表现为破骨细胞增加 ;电镜观察骨细胞呈吸收相。继续跑跳训练( 3 -4周 )可使疲劳向损伤转化 ,X线出现轻微骨膜反应 ,核素骨显像呈现阳性 ,血生化及组织学出现应力性损伤的变化。结论 :运动性骨疲劳的发生是一个由骨细胞直接参与的破骨细胞性重吸收大于成骨细胞性骨形成的生理过程 ;高血PTH、高血BGP和低血T是其发生发展过程中的血生化基础     

钛-6铝-4钒颗粒对破骨细胞形态和功能的影响

目的在体外条件下观察钛-6铝-4钒（Ti-6AL-4V）颗粒对破骨细胞形态和功能的影响。方法取新西兰大耳兔破骨细胞培养在玻璃盖玻片和牛皮质骨片上，实验组用0．1mg／ml颗粒刺激，经不同时段培养后行抗酒石酸酸性磷酸酶（TRAP）染色，观察颗粒对破骨细胞形态的影响。对骨片上形成的骨吸收陷窝进行甲苯胺蓝染色观察，并用计算机图像分析软件评估吸收面积的大小。结果破骨细胞可以吞噬颗粒，形态变得不规则，特征性TRAP染色加深，较早出现凋亡征象。经颗粒刺激后在骨片上形成的骨吸收陷窝面积较大、数量较多。结论破骨细胞有吞噬功能，吞噬Ti-6AL-4V颗粒后发生形态和功能的变化，骨吸收功能增强。     

On possible mechanisms of osteopenia in humans in microgravity and situations imitating its effects

The review deals with the analysis of osteodensitometry data from the cosmonauts flown on Russian space station MIR and the International space station and suppositions about involvement of different levels of metabolism regulation in bone loss triggered by insufficient mechanic loading in microgravity attendant by redistribution of body liquids. It is surmised that the initial reactions are associated with the biomechanical factor and recruitment of local mechanisms, i.e. osteocyte osteolysis and inhibition of osteoblast histogenesis. Regulation on the level of tissues and organs is responsible for destabilization of calcium homeostasis (low calcium absorption in the intestine and readsorption in the kidney). Changes in the hierarchy of ion and volume regulation may provoke osteoclast resorption which further increases osteopenia.     

Fra-1原癌基因研究进展

原癌基因Fra-1是核转录因子AP-1家族的成员，通过亮氨酸拉链结构域与Jun蛋白形成异源二聚体，调控靶基因的转录。在胚胎发育过程中，通过促进成骨细胞、破骨细胞分化，影响骨基质蛋白的合成，参与骨形成。近年来，发现Fra-1在恶性肿瘤的迁徙、侵袭中发挥着重要的作用，其可能成为肿瘤治疗的新靶点。本文综述了Fra-1在骨形成及肿瘤中的研究进展。     

Carbon-11 labeled cathepsin K inhibitors: Syntheses and preliminary in vivo evaluation

Cathepsin K is a cysteine peptidase primarily located in osteoclasts, cells involved in normal growth and remodeling of bone but that are also responsible for bone loss in osteolytic diseases such as osteoporosis. In vivo imaging of cathepsin K may provide a method to assess changes in osteoclast numbers in such disease states. To that end, two high-affinity and selective cathepsin K inhibitors were radiolabeled with carbon-11. In vivo microPET imaging studies demonstrated uptake and prolonged retention of radioactivity in actively growing or remodeling bone regions (e.g., distal ulnar, carpal, distal and proximal humeral, distal femur, proximal tibia, tail vertebrae). Uptake into bone could be blocked by pre- or co-injection of unlabeled ligand, supporting a specific and saturable binding mechanism for radiotracer localization. These proof-of-concept studies indicate that radiolabeled cathepsin K inhibitors may have potential as in vivo imaging radiotracers for assessing changes of osteoclast numbers in osteolytic diseases.     

Clinical utility of biochemical marker of bone remodelling in patients with bone metastases of solid tumors.

Bone turnover is characterized both by the formation of new bone by the osteoblasts and the resorption of old tissue by the osteoclast. This process takes place only on the surface of bone and can be described in terms of spatio-temporal events that are the bone metabolic unit and the bone remodelling cycle. The former consists of a discrete group of cells (osteoblasts and osteoclasts) involved in a particular remodelling event while the latter represents the succession of resorption and formation. In a typical remodelling cycle, resorption takes 7-10 days, whereas formation requires 2-3 months. Remodelling is regulated either by local or systemic factors, including electrical and mechanical forces, hormones (e.g. parathyroid hormone, sexual steroids, calcitriol, cortisol, thyroid hormones, calcitonin), growth factors and cytokines. Recently different circulating biochemical markers have been proposed for the investigation of bone turnover. In addition to classical parameters such as serum alkaline phosphatase and urinary calcium and hydroxyproline, new markers have gained clinical attention because of their accuracy in assessing the dynamic changes in bone remodelling (bone alkaline phosphatase, osteocalcin, propeptides PICP and PINP, tartrate-resistant acid phosphatase, deoxypyridinoline, pyridinoline, telopeptide CTx and NTx). The aim of this review is to present the recent advances in this field and the clinical application of markers of bone turnover in patients with bone metastases from solid tumors. Also the cellular and molecular bases of bone remodelling are reported with details.     

Stress fracture of the tarsal navicular

Stress fractures of the lower extremity are common among military members and athletes at all levels of participation. They typically occur when an individual begins a new or different type of physical training or during periods of abrupt increase in the level of training. Stress fractures represent an incomplete remodeling of bone that occurs secondary to repetitive mechanical loading. In response to this increased loading, the osteoclastic resorption of lamellar bone outpaces the ability of the osteoblasts to create new lamellar bone, eventually leading to structural failure. The following case report reviews the typical clinical presentation, imaging findings, and treatment of the tarsal navicular stress fracture.     

阻断PI3K信号通路显著抑制成骨前体细胞MC3T3-E1的分化

目的：研究PI3K信号通路对成骨前体细胞MC3T3-E1分化的调控作用。方法：首先通过Western印迹试验检测到PI3K信号通路参与成骨细胞分化的调控。应用PI3K激酶的特异性抑制剂LY294002药物阻断PI3K信号通路的活化，通过碱性磷酸酶(ALP)和von Kossa染色观察成骨前体细胞MC3T3-E1分化的改变。结果：Western印迹试验显示，成骨细胞分化过程中PI3K信号通路明显活化。阻断该信号通路的活化显著抑制成骨细胞碱性磷酸酶的活性，同时降低成骨细胞体外形成骨结节结构的能力。结论：PI3K信号通路参与了成骨细胞分化的调控，而这种调控作用是成骨细胞分化所必需的。     

电离辐射对原代成骨细胞M-CSF表达的影响

目的 研究辐射对于原代成骨细胞巨噬细胞集落刺激因子（M-CSF）表达的影响,进而研究辐射导致骨损伤的分子机理。 方法 采用原代骨髓间充质干细胞诱导分化为成骨细胞,经0、2、4 Gy 137Cs γ射线照射后,采用实时定量PCR以及Western blot方法检测辐射对M-CSF mRNA和蛋白表达水平的影响。 结果 2 Gy和4 Gy γ射线照射均能引起成骨细胞M-CSF mRNA（t=-17.329, P < 0.01;t=-3.841, P < 0.05）和蛋白表达水平上调。4 Gy照射后则会导致成骨前体细胞M-CSF mRNA表达水平上调（t=-4.478, P < 0.05）,但与对照组比较,两者的蛋白表达水平未见显著差异。 结论 2 Gy和4 Gy γ射线照射后,成骨细胞M-CSF表达水平上调能增强核因子κB受体活化因子配体对破骨细胞分化、成熟的促进作用,有助于增强破骨细胞的骨吸收能力。     

不同强度运动对去卵巢大鼠骨量的影响及其机理

以成年SD大鼠去卵巢建立骨质疏松模型,用骨形态计量学方法,研究了8周的大强度和中等强度(分别为20m/min和30m/min,1h/day,5d/week)跑台运动对大鼠胫骨近心干骺端松质骨骨量的影响.结果去卵巢安静组大鼠骨量减少(%Tb.Ar-75%,p＜0.01;Tb.N-74%,p＜0.01),骨形成增加(BFB/BS+115%,BFR/BV+123%,P＜0.01)、骨吸收增加(Oc.No+229%,p＜0.01),为高转换型的骨代谢.中等强度运动的去卵巢大鼠比去卵巢安静大鼠骨形成减少(%L.Pm-42%,BFR/BS-36%,P＜0.05),骨吸收减少(Oc.No-42%,p＜0.05),高转换受到抑制,骨量增加(%Tb.Ar+53%,p＜0.05;Tb.N+69%,p＜0.01),但仍比正常组大鼠骨量降低(%Tb.Ar-61%,p＜0.01).去卵巢后大强度运动与去卵巢安静组大鼠各项指标相比无显著性差异(p＞0.05),与中等强度运动比骨形成增加(BFR/BS+121%,P＜0.01),骨吸收增加(Oc.No+103%,p＜0.05),骨量减少(%Tb.Ar-37%,p＜0.05),仍为高转换型骨代谢.结论大鼠去卵巢后中等强度运动通过抑制高骨转换可减少骨丢失,减轻骨质疏松的程度,大强度运动对减轻骨质疏松的程度无作用.     

Effect of exercise on bone: permissive influence of estrogen and calcium

Estrogen deficiency in postmenopausal women is associated with low lumbar bone mineral density and an increased incidence of fractures of the vertebrae and proximal femur. Estrogen deficiency in premenopausal women with secondary amenorrhea related to athletic training or anorexia nervosa is also associated with decreased lumbar bone mineral density. The purpose of this review is to present four concepts related to the adaptations of bone to physical exercise, as a basis to explain the loss of bone mass in women with athletic amenorrhea. These concepts are based on Lanyon's theory of a Minimum Effective Strain-Related Stimulus. The bone remodeling response to estrogen deficiency is an increase in the rate of bone remodeling activity and in the rate of bone resorption relative to formation, resulting in a net loss of bone mass. In the presence of estrogen deficiency, the stimulus of physical activity is thought first to decrease the rate of turnover and secondly to increase bone formation. Endurance exercise training appears to be an insufficient stimulus to accomplish both tasks, which may explain why these athletes often have low lumbar bone mineral density.     

Correlations between uptake of technetium, calcium, phosphate, and mineralization in rat tibial bone repair

Technetium-99m-(99mTc) phosphates are extensively used for detection of bone formation and resorption. The present is a study of 99mTc incorporation during bone remodeling. Uptake of 99mTc-labeled phosphate was studied in an animal model of primary osteogenesis following tibial marrow injury and incorporation was correlated to that of calcium-47 (47Ca), phosphorus-32 (32P), and with matrix vesicle calcification. Isotope uptake on Day 6 in the whole bone was increased compared to controls. On this day, an increase in vesicular diameter and distance from the calcified front was previously observed. Technetium-99m-labeled phosphates were detected only in the organic phase. Phosphorus-32 and 47Ca were detected in both organic and inorganic phases. It is suggested that 99mTc serves as a specific marker to the anabolic phase of remodeling. Increased incorporation of 99mTc during bone healing indicates enhanced organic matrix formation and not calcification.     

微重力对成骨细胞及其分化过程的影响

目的 综述近年来有关微重力导致骨丢失的最新研究进展. 资料来源与选择 国内外该领域的相关文献. 资料引用 资料引用文献40篇. 资料综合 详细描述了微重力对成骨细胞增殖、分化的影响.着重介绍了微重力对骨髓间质干细胞到成熟成骨细胞整个分化过程的影响及其可能机制. 结论 微重力不但影响成骨细胞的增殖和活性,也影响骨髓间质干细胞骨向分化过程,导致成熟成骨细胞的数量减少和活性下降,引起空间骨丢失.     

The osteoclast—what’s new?

Bone resorption is required for skeletal modelling during bone growth and for mineral homeostasis and bone remodelling throughout life. Osteoclasts are multinucleated cells that are uniquely specialised to carry out this physiological bone resorption. As osteolysis is a feature of most diseases of bone and joint, osteoclasts also play a role in pathological bone resorption, the extent of which is a function of the cellular and molecular mechanisms that govern their formation and function.     

Bone healing during lower limb lengthening by distraction epiphysiolysis

A study of limb lengthening by distraction epiphysiolysis in the rabbit tibia is presented. A special external distraction device was developed that allowed 10 mm lengthening of the leg. Bone formation in the elongated zone was studied by computed tomography and [99mTc] methylene diphosphonate (MDP) scintigraphy. Computed tomography showed bone formation proceeding for several weeks after the end of the distraction period, followed by a decrease in the amount of bone during a remodeling phase leading to the formation of a solid cortical structure. The uptake of [99mTc]MDP increased parallel to, but preceeding the actual accretion of bone, followed by a decrease during the bone remodeling phase. Uptake of the tracer will partly reflect bone metabolism, but other factors, like trauma, determine much of the uptake.     

力学拉伸强度对破骨细胞形成和分化的影响

目的 探讨早期力学拉伸强度对破骨细胞形成和分化的影响. 方法 对采用巨噬细胞集落刺激因子和破骨细胞分化因子诱导的RAW 264.7细胞分别施加0,1 000,1 500,2 000,2 500和5 000με的力学拉伸3 d.于培养第7天观察各组破骨细胞形态、计数及检测前体细胞增殖,并于培养第4,7天检测各组细胞培养液中抗酒石酸酸性磷酸酶(TRAP)活性. 结果 2 500με组的破骨细胞形成数量明显减少,5 000με组的破骨细胞数量显著增加;2 000,2 500 με组前体细胞增殖明显,5 000με组前体细胞增殖显著降低;1 000,1 500με组与静态组在破骨细胞形成数量和前体细胞增殖方面差异无统计学意义.与静态组相比,应变组第4,7天培养液的破骨细胞TRAP活性均降低. 结论 早期力学因素可直接影响破骨细胞的形成和分化,较高强度的生理载荷可抑制破骨细胞形成,病理过载促进破骨细胞的形成,而低强度载荷几乎不影响破骨细胞形成;早期力学载荷可抑制破骨细胞分化.     

失重对成骨细胞基因表达和细胞功能影响的研究进展

骨骼可以适应包括重力在内的各种机械刺激，并对骨形成与骨吸收之间的平衡进行调整。失重状态下的骨质减少主要归因于骨形成的减少，这与成骨细胞功能下降有关，表现为细胞增殖粘附能力下降，与分化成熟相关的物质(碱性磷酸酶，骨钙素和I型胶原)的mRNA及蛋白合成均减少，多种生长因子的分泌量以及细胞对其反应性下降。成骨细胞功能下降的机制尚不明确，有假说认为失重时细胞形态的改变导致了基因表达与功能的变化。