早期骨关节炎软骨下骨微结构改变和骨改建相关基因表达研究
发布时间：2019-02-22 12:03
【摘要】：骨关节炎是一种常见的疾病,在全身各关节均可发生,可引起严重的疼痛和功能障碍,包括颞下颌关节。颞下颌关节紊乱是口腔医学领域的常见病、多发病,发病率为11.4%~58.0%,平均年龄在30.2~39.6岁,女性患者约是男性患者的3.3倍,随患者年龄的增加其发病率逐渐增高,60岁以上的患者,80%出现过TMJOA的症状,其临床症状主要为关节区疼痛、关节运动功能障碍、关节弹响及杂音等,患者的身体健康和生活质量受到严重影响。颞下颌关节骨关节炎是颞下颌关节紊乱的一种重要的类型,其主要的病理改变是关节软骨的退化,并且伴有软骨下骨硬化和骨赘的形成。大量实验结果表明,通过细胞因子调控软骨下骨的骨重塑能够延缓关节软骨的退化。目前临床治疗颞下颌关节骨关节炎的方式主要包括非手术方案,如物理疗法,佩戴咬合垫,非甾体抗炎药的使用,和关节注射润滑液或皮质类固醇等。治疗的目的旨在缓解症状,阻止颞下颌关节疾病进展和恢复颞下颌关节的功能。近些年来,国内外在OA和TMJOA的研究上取得了重大进展,但其病因、发展过程,以及发病机制仍需进一步探讨。以往研究对关节软骨的改变在OA中的作用进行了大量的研究,对软骨下骨的研究较少。近来有学者提出,软骨下骨在骨关节炎中可能早于关节软骨的退变。软骨下骨与关节软骨作为关节整体的一部分,在解剖结构上相互依存,而关节软骨的破坏与软骨下骨的改变检测指标灵敏度不同,很难说清两者之间谁为始发因素。尽管软骨下骨的改变在OA中是否早于关节软骨的退变尚未得到明确的结论,但可以肯定的是,软骨下骨在骨关节炎的病理变化过程中必然发生改变。以往的研究主要集中在关节软骨的破坏及机制上,对软骨下骨在早期骨关节炎中的改变研究较少。越来越多的研究表明软骨下骨在骨关节炎的发生发展中有重要作用,为探索骨关节炎的研究和治疗提供了新的方向。综上所述,本实验拟先建立SD大鼠早期骨关节炎实验动物模型,通过影像学和组织病理学技术研究软骨下骨在早期骨关节炎中的微结构改变,了解软骨下骨和关节软骨在早期骨关节炎中的改变,最后通过检测骨改建相关基因在早期骨关节炎中的表达差异,了解骨形成与骨吸收相关基因在早期骨关节炎软骨下骨的表达变化。为检测软骨下骨的微结构改变诊断早期骨关节炎和通过干扰软骨下骨的骨改建过程治疗骨关节炎提供一定的实验依据。本实验的主要研究结果和结论如下:1、通过MMT手术成功制作早期骨关节炎实验动物模型。术后3周,MMT侧关节软骨面无破损,灰白,失去原有光泽,假手术侧关节面正常。表明MMT术能造成关节的退变。2、利用Micro-CT影像学手段对实验动物早期骨关节炎软骨下骨进行三维重建、分析,MMT侧软骨下骨小梁骨的骨体积分数(BV/TV)降低、骨小梁厚度(Tb.Th)降低、骨小梁连接密度(Conn.D)降低(P0.05),骨小梁间距(Tb.Sp)增加(P0.05),骨小梁数目(Tb.N)减少(P0.05)。术后3周组织病理学切片中,软骨未见明显退变,软骨下骨小梁稀疏,未见边缘骨赘的形成。表明早期骨关节炎中软骨下骨量轻微降低。3、软骨下骨改建相关基因检测,Rt-PCR结果显示,术后3周软骨下骨的成骨细胞相关基因(ALP、RUNX2、OCN)大量表达,MMT侧小于假手术侧(P0.05),表明骨形成降低。破骨细胞相关基因(TRAP、CTSK、MMP9)表达升高,且MMT侧高于假手术侧(P0.01)。结果表明在早期骨关节炎中,软骨下骨改建较活跃,骨吸收功能增强,骨形成功能降低,骨吸收与骨形成失去平衡,导致软骨下骨的微结构发生改变。
[Abstract]:Osteoarthritis is a common disease that can occur in all joints of the body, causing severe pain and dysfunction, including lower jaw joints. The disorder of the mandibular joint is a common disease in the field of stomatology. The incidence rate is 11. 4% ~ 58. 0%. The average age is 30. 2 ~ 39. 6 years. The female patients are about 3. 3 times of the male patients, and the incidence of the patients with the age of the patients increases gradually, and the incidence of the patients over 60 years of age and 80% have the symptoms of TMJOA. The clinical symptoms of the patient are joint area pain, joint motion dysfunction, joint ejection and noise, and the patient's health and quality of life are seriously affected. Mandibular joint osteoarthritis is an important type of the mandibular joint disorder. The main pathological changes are the degeneration of the articular cartilage and the formation of the subchondral bone and osteophyte. The results show that the bone remodeling of the subchondral bone can delay the degeneration of the articular cartilage. Currently, the method of clinical treatment of the mandibular joint osteoarthritis mainly comprises the non-operative scheme, such as physical therapy, wearing the bite pad, the use of the non-implant anti-inflammatory agent, the joint injection lubricating fluid or the corticosteroid, and the like. The purpose of the treatment is to relieve symptoms, to prevent the progression of mandibular joint disease and to restore the function of the lower jaw joint. In recent years, significant progress has been made in the research of OA and TMJOA at home and abroad, but the cause, the development process and the mechanism of the pathogenesis still need to be further explored. Previous studies have done a lot of research on the changes of articular cartilage in OA, and less research on the subchondral bone. Recently, some scholars have suggested that the subchondral bone may be early in the degenerative changes of the articular cartilage in osteoarthritis. The subchondral bone and articular cartilage, as part of the joint, are interdependent on the anatomical structure, and the damage of the articular cartilage is different from that of the subchondral bone, and it is difficult to say who is the initiating factor. Although the change of the subchondral bone is not well-defined in OA as early as the change of the articular cartilage, it is confirmed that the subchondral bone inevitably changes in the course of the pathological change of the osteoarthritis. Previous studies have focused on the destruction and mechanism of the articular cartilage, and the change of the subchondral bone in the early stage of osteoarthritis is less. More and more studies have shown that the subchondral bone plays an important role in the development of osteoarthritis and provides a new direction for the research and treatment of osteoarthritis. To sum up, this experiment is to establish an experimental animal model of early osteoarthritis of SD rats, and to study the changes of the subchondral bone in early osteoarthritis by imaging and histopathology, and to understand the changes of the subchondral bone and the articular cartilage in the early osteoarthritis. Finally, the expression of bone formation and bone resorption related genes in early osteoarthritis was studied by detecting the difference in the expression of bone remodeling related genes in early osteoarthritis. In order to detect the microstructural changes of the subchondral bone, an experimental basis is provided for the diagnosis of early osteoarthritis and for the treatment of osteoarthritis by means of the bone remodeling process that interferes with the subchondral bone. The main results and conclusions of this experiment are as follows: 1. The experimental animal model of early osteoarthritis was successfully prepared by MMT. At 3 weeks after operation, the articular surface of the articular cartilage on the side of the MMT was not damaged, and the articular surface on the side of the artificial operation side was normal. The bone volume fraction (BV/ TV) of the subchondral bone of the subchondral bone was reduced, and the thickness of the small beam (Tb. Th) was reduced. The connection density (Conn. D) of the bone small beam was decreased (P0.05), the space of the bone small beam (Tb. Sp) was increased (P0.05), and the number of the bone small beams (Tb. N) was decreased (P0.05). In the 3-week postoperative pathological section, the cartilage was not seen to be obviously retrograded, and the subchondral bone small beam was sparse, and the formation of the edge osteophyte was not found. The results showed that the amount of bone in the subchondral bone was slightly decreased in the early stage of osteoarthritis. The results of the Rt-PCR showed that the osteoblast-related gene (ALP, RUNX2, OCN) of the subchondral bone in the 3-week post-operation was significantly higher than that of the sham-operated side (P <0.05), indicating that the bone formation decreased. The expression of osteoclast-related gene (TRAP, CTSK, MMP9) increased and the MMT side was higher than that of the sham-operated side (P0.01). The results show that in the early stage of osteoarthritis, the subchondral bone remodeling is more active, the bone resorption function is enhanced, the bone formation function is reduced, the bone absorption and the bone formation lose balance, and the microstructure of the subchondral bone is changed.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R684.3
本文编号：2428206
[Abstract]:Osteoarthritis is a common disease that can occur in all joints of the body, causing severe pain and dysfunction, including lower jaw joints. The disorder of the mandibular joint is a common disease in the field of stomatology. The incidence rate is 11. 4% ~ 58. 0%. The average age is 30. 2 ~ 39. 6 years. The female patients are about 3. 3 times of the male patients, and the incidence of the patients with the age of the patients increases gradually, and the incidence of the patients over 60 years of age and 80% have the symptoms of TMJOA. The clinical symptoms of the patient are joint area pain, joint motion dysfunction, joint ejection and noise, and the patient's health and quality of life are seriously affected. Mandibular joint osteoarthritis is an important type of the mandibular joint disorder. The main pathological changes are the degeneration of the articular cartilage and the formation of the subchondral bone and osteophyte. The results show that the bone remodeling of the subchondral bone can delay the degeneration of the articular cartilage. Currently, the method of clinical treatment of the mandibular joint osteoarthritis mainly comprises the non-operative scheme, such as physical therapy, wearing the bite pad, the use of the non-implant anti-inflammatory agent, the joint injection lubricating fluid or the corticosteroid, and the like. The purpose of the treatment is to relieve symptoms, to prevent the progression of mandibular joint disease and to restore the function of the lower jaw joint. In recent years, significant progress has been made in the research of OA and TMJOA at home and abroad, but the cause, the development process and the mechanism of the pathogenesis still need to be further explored. Previous studies have done a lot of research on the changes of articular cartilage in OA, and less research on the subchondral bone. Recently, some scholars have suggested that the subchondral bone may be early in the degenerative changes of the articular cartilage in osteoarthritis. The subchondral bone and articular cartilage, as part of the joint, are interdependent on the anatomical structure, and the damage of the articular cartilage is different from that of the subchondral bone, and it is difficult to say who is the initiating factor. Although the change of the subchondral bone is not well-defined in OA as early as the change of the articular cartilage, it is confirmed that the subchondral bone inevitably changes in the course of the pathological change of the osteoarthritis. Previous studies have focused on the destruction and mechanism of the articular cartilage, and the change of the subchondral bone in the early stage of osteoarthritis is less. More and more studies have shown that the subchondral bone plays an important role in the development of osteoarthritis and provides a new direction for the research and treatment of osteoarthritis. To sum up, this experiment is to establish an experimental animal model of early osteoarthritis of SD rats, and to study the changes of the subchondral bone in early osteoarthritis by imaging and histopathology, and to understand the changes of the subchondral bone and the articular cartilage in the early osteoarthritis. Finally, the expression of bone formation and bone resorption related genes in early osteoarthritis was studied by detecting the difference in the expression of bone remodeling related genes in early osteoarthritis. In order to detect the microstructural changes of the subchondral bone, an experimental basis is provided for the diagnosis of early osteoarthritis and for the treatment of osteoarthritis by means of the bone remodeling process that interferes with the subchondral bone. The main results and conclusions of this experiment are as follows: 1. The experimental animal model of early osteoarthritis was successfully prepared by MMT. At 3 weeks after operation, the articular surface of the articular cartilage on the side of the MMT was not damaged, and the articular surface on the side of the artificial operation side was normal. The bone volume fraction (BV/ TV) of the subchondral bone of the subchondral bone was reduced, and the thickness of the small beam (Tb. Th) was reduced. The connection density (Conn. D) of the bone small beam was decreased (P0.05), the space of the bone small beam (Tb. Sp) was increased (P0.05), and the number of the bone small beams (Tb. N) was decreased (P0.05). In the 3-week postoperative pathological section, the cartilage was not seen to be obviously retrograded, and the subchondral bone small beam was sparse, and the formation of the edge osteophyte was not found. The results showed that the amount of bone in the subchondral bone was slightly decreased in the early stage of osteoarthritis. The results of the Rt-PCR showed that the osteoblast-related gene (ALP, RUNX2, OCN) of the subchondral bone in the 3-week post-operation was significantly higher than that of the sham-operated side (P <0.05), indicating that the bone formation decreased. The expression of osteoclast-related gene (TRAP, CTSK, MMP9) increased and the MMT side was higher than that of the sham-operated side (P0.01). The results show that in the early stage of osteoarthritis, the subchondral bone remodeling is more active, the bone resorption function is enhanced, the bone formation function is reduced, the bone absorption and the bone formation lose balance, and the microstructure of the subchondral bone is changed.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R684.3
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