Correlation of osteoblasts and osteoclasts with alcohol-induced femoral head necrosis: a new strategy of prevention and target therapy

doi:10.3969/j.issn.2095-4344.2016.46.017

Abstract

Abstract:

BACKGROUND: Alcohol-induced femoral head necrosis is a bone metabolism disease that involves a series of alcoholism-induced pathological changes, including degeneration, necrosis and deposition of adipocytes and osteoporosis, and trabecular collapse in the subchondral bone trabeculae of the femoral head.
OBJECTIVE: To introduce the correlation of osteoblasts and osteoclasts with alcohol-induced femoral head necrosis.
METHODS: The first author searched relative articles in PubMed and CNKI databases published before May 2016 using the keywords of “osteoblast, osteoclast, alcohol-induced ONFH, bone metabolism” in English and Chinese, respectively. 133 literatures were retrieved and 38 literatures were in accordance with the inclusion criteria.
RESULTS AND CONCLUSION: During the process of bone metabolism, osteoblasts and osteoclasts exhibit interaction in term of cell number and viability. In-depth study on osteoblasts, osteoclasts and their interaction cannot only give insight into the pathogenesis and repair of alcohol-induced femoral head necrosis, but also provide new ideas and strategies for prevention and target treatment of bone metabolic diseases.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Osteoblasts, Osteoclasts, Femur Head Necrosis, Metabolism, Tissue Engineering

CLC Number:

R318

Chen Jun-yu, Wang Jian-zhong. Correlation of osteoblasts and osteoclasts with alcohol-induced femoral head necrosis: a new strategy of prevention and target therapy[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(46): 6963-6969.

Figures/Tables 2

2.1 酒精性股骨头坏死及其病理学基础 2.1.1 酒精性股骨头坏死概述股骨头坏死患者中有10%)74%是由于长期大量饮酒造成的，即酒精性股骨头坏死[14-18]。酒精性股骨头坏死是一种难治性非创伤性股骨头坏死。该病的发生主要由于长期大量饮酒造成脂代谢异常，骨髓间充质干细胞分化成骨细胞及破骨细胞异常，从而造成骨吸收与骨形成的动态平衡紊乱，最终导致股骨头缺血坏死[19-20]。随着饮酒已成为一个全球性的危害人体健康的因素，世界卫生组织(WHO)指出大量酗酒是酒精性股骨头坏死的重要发病因素之一，而且在世界范围内其发病率呈上升趋势，其患病人数占非创伤性股骨头坏死的比重也越来越大，北京积水潭医院在1996)2000年间对306例成人非创伤性股骨头坏死调研发现其中46%是由过量饮酒引起的，超过激素引起的股骨头坏死(占34%)[21]。早期酒精性股骨头坏死患者常感患肢无力，髋关节疼痛，慢性钝痛或剧痛，夜间和劳累加重，可放射到膝关节、大腿内侧、腹股沟等；到了中晚期酒精性股骨头坏死时，患者出现髋关节功能活动受限，以外展、内旋及屈曲等功能主。下蹲、穿鞋困难、行走步幅小、跛行、4字实验、托马氏征阳性及患侧下肢肌肉萎缩。治疗不及时者最终发生股骨头缺血性坏死且一旦发生很难逆转。 2.1.2 酒精性股骨头坏死的病理学变化酒精性股骨头坏死的病理学变化是由多种因素综合作用的结果，已熟知的有关酒精性股骨头坏死的病理机制如脂质代谢紊乱，骨质疏松，凝血异常，脂肪栓塞，骨内高压，骨细胞脂肪变性，骨髓基质细胞成脂分化及骨代谢等假说[22]，且假说中多涉及酒精所引起的脂肪代谢紊乱为主的病理过程。随着细胞生物学的不断深入研究，从细胞生物学及细胞代谢角度分析，该病的病理过程可概括为：大量的酒精摄入导致血脂代谢异常、股骨头髓内脂肪细胞增殖，引起脂肪细胞分化增加及变性坏死并沉积于股骨头软骨下的骨细胞内；另外，酒精刺激使骨髓间充质干细胞分化成骨细胞异常，则会影响体内成骨/破骨细胞紊乱，影响破骨细胞介导的骨吸收与成骨细胞介导的骨形成过程，影响死骨清除与骨组织重建进程，引起骨循环中断、骨的活性成分死亡及随后修复的一系列复杂病理过程，进而导致骨小梁断裂，股骨头关节软骨进行性塌陷，股骨头血液灌注量减少，引发股骨头坏死[19-20]。 2.2 成骨细胞、破骨细胞及其在骨代谢中的生物学功能成骨细胞与破骨细胞是骨重建过程中的两种主要细胞，二者相互作用、相互影响，调节成骨细胞与破骨细胞的生成比例与生物活性，调控骨吸收与骨形成的动态平衡，影响骨代谢。 2.2.1 成骨细胞及其生物学功能成骨细胞，即可产生骨质或基质的细胞，是参与骨形成和骨坏死后修复的主要功能细胞。成骨细胞在骨组织的生长发育、骨代谢动态平衡、骨形成、及骨损伤后的重建修复过程中都起重要作用，是参与骨形成的关键细胞，见图2。成骨细胞在骨形成过程中要经历4个阶段，即细胞增殖分化、细胞外基质成熟、细胞外基质矿化和细胞凋亡，尤其以成骨细胞分化为骨发生与骨形成、骨重建的前提。其主要的生物学功能可概括为以下3点：①负责骨基质的合成、分泌及矿化；②调控破骨细胞的骨吸收功能；③与破骨细胞共同维持骨代谢平衡。"

成骨细胞的来源是多源的，据可靠研究证明，颅骨或胚胎颅骨、骨膜源性细胞及间充质干细胞都具有很强的分化成骨细胞的能力[23-27]，其中以间充质干细胞的分化为主要来源。使用光镜或者电镜可以观察到成骨细胞的主要形态学特征：在光镜下成骨细胞一般呈现出锥形、圆形或立方形，细而短的突起从成骨细胞伸出与邻近的细胞相连，细胞核大而圆且位于细胞的一端，线粒体形态细长且分散存在于细胞浆内；在电镜下，粗面内质网基本占据了成骨细胞的包浆，形成一个由核糖体附着的膜状管形物。正常情况下，圆形或细长的线粒体黏附于粗面内质网上且部分线粒体中含有矿化小粒。 2.2.2 破骨细胞及其生物学功能破骨细胞又称为骨吸收细胞(bone-resorbing cells)，是骨组织成分的一种，行使骨吸收的功能。破骨细胞属于单核巨噬细胞，其细胞内有2-20个不等的细胞核，但多数情况下每个细胞内含有10-20个细胞核。此外，破骨细胞内含有大量溶酶体、广泛分布于近核区的高尔基体、众多游离的核糖体与少量的粗面内质网，还有伪足及突起的形态不规则的细胞，见图3。在电镜下观察可发现破骨细胞的褶皱膜含有很多构成完全不同的亚结构，这些亚结构相互作用配合，保证破骨细胞介导的骨吸收过程的顺利进行[28]。破骨细胞是人体惟一具有溶解骨组织能力的细胞，在骨重建中有重要作用。高表达抗酒石酸酸性磷酸酶和组织蛋白酶K是破骨细胞的主要标志。破骨细胞的起源与成骨细胞完全不同，是由起源于骨髓造血系统的特定的破骨细胞前体在趋化因子的作用下进入血液循环，到达处于骨吸收状态的骨组织部位，即骨重建单位时，在一系列趋化因子与细胞因子的作用下进入骨组织并分化成为成熟的破骨细胞。其介导的骨吸收功能在人体骨组织重建、维持骨骼系统完整性、骨组织内矿物质稳态及维持骨代谢平衡中均发挥关键作用。此外，破骨细胞还与局部性或者全身性骨质疏松、坏死有关。"

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