早期骨關節(jié)炎軟骨下骨微結構改變和骨改建相關基因表達研究
發(fā)布時間：2019-02-22 12:03
【摘要】：骨關節(jié)炎是一種常見的疾病,在全身各關節(jié)均可發(fā)生,可引起嚴重的疼痛和功能障礙,包括顳下頜關節(jié)。顳下頜關節(jié)紊亂是口腔醫(yī)學領域的常見病、多發(fā)病,發(fā)病率為11.4%~58.0%,平均年齡在30.2~39.6歲,女性患者約是男性患者的3.3倍,隨患者年齡的增加其發(fā)病率逐漸增高,60歲以上的患者,80%出現(xiàn)過TMJOA的癥狀,其臨床癥狀主要為關節(jié)區(qū)疼痛、關節(jié)運動功能障礙、關節(jié)彈響及雜音等,患者的身體健康和生活質量受到嚴重影響。顳下頜關節(jié)骨關節(jié)炎是顳下頜關節(jié)紊亂的一種重要的類型,其主要的病理改變是關節(jié)軟骨的退化,并且伴有軟骨下骨硬化和骨贅的形成。大量實驗結果表明,通過細胞因子調控軟骨下骨的骨重塑能夠延緩關節(jié)軟骨的退化。目前臨床治療顳下頜關節(jié)骨關節(jié)炎的方式主要包括非手術方案,如物理療法,佩戴咬合墊,非甾體抗炎藥的使用,和關節(jié)注射潤滑液或皮質類固醇等。治療的目的旨在緩解癥狀,阻止顳下頜關節(jié)疾病進展和恢復顳下頜關節(jié)的功能。近些年來,國內外在OA和TMJOA的研究上取得了重大進展,但其病因、發(fā)展過程,以及發(fā)病機制仍需進一步探討。以往研究對關節(jié)軟骨的改變在OA中的作用進行了大量的研究,對軟骨下骨的研究較少。近來有學者提出,軟骨下骨在骨關節(jié)炎中可能早于關節(jié)軟骨的退變。軟骨下骨與關節(jié)軟骨作為關節(jié)整體的一部分,在解剖結構上相互依存,而關節(jié)軟骨的破壞與軟骨下骨的改變檢測指標靈敏度不同,很難說清兩者之間誰為始發(fā)因素。盡管軟骨下骨的改變在OA中是否早于關節(jié)軟骨的退變尚未得到明確的結論,但可以肯定的是,軟骨下骨在骨關節(jié)炎的病理變化過程中必然發(fā)生改變。以往的研究主要集中在關節(jié)軟骨的破壞及機制上,對軟骨下骨在早期骨關節(jié)炎中的改變研究較少。越來越多的研究表明軟骨下骨在骨關節(jié)炎的發(fā)生發(fā)展中有重要作用,為探索骨關節(jié)炎的研究和治療提供了新的方向。綜上所述,本實驗擬先建立SD大鼠早期骨關節(jié)炎實驗動物模型,通過影像學和組織病理學技術研究軟骨下骨在早期骨關節(jié)炎中的微結構改變,了解軟骨下骨和關節(jié)軟骨在早期骨關節(jié)炎中的改變,最后通過檢測骨改建相關基因在早期骨關節(jié)炎中的表達差異,了解骨形成與骨吸收相關基因在早期骨關節(jié)炎軟骨下骨的表達變化。為檢測軟骨下骨的微結構改變診斷早期骨關節(jié)炎和通過干擾軟骨下骨的骨改建過程治療骨關節(jié)炎提供一定的實驗依據(jù)。本實驗的主要研究結果和結論如下:1、通過MMT手術成功制作早期骨關節(jié)炎實驗動物模型。術后3周,MMT側關節(jié)軟骨面無破損,灰白,失去原有光澤,假手術側關節(jié)面正常。表明MMT術能造成關節(jié)的退變。2、利用Micro-CT影像學手段對實驗動物早期骨關節(jié)炎軟骨下骨進行三維重建、分析,MMT側軟骨下骨小梁骨的骨體積分數(shù)(BV/TV)降低、骨小梁厚度(Tb.Th)降低、骨小梁連接密度(Conn.D)降低(P0.05),骨小梁間距(Tb.Sp)增加(P0.05),骨小梁數(shù)目(Tb.N)減少(P0.05)。術后3周組織病理學切片中,軟骨未見明顯退變,軟骨下骨小梁稀疏,未見邊緣骨贅的形成。表明早期骨關節(jié)炎中軟骨下骨量輕微降低。3、軟骨下骨改建相關基因檢測,Rt-PCR結果顯示,術后3周軟骨下骨的成骨細胞相關基因(ALP、RUNX2、OCN)大量表達,MMT側小于假手術側(P0.05),表明骨形成降低。破骨細胞相關基因(TRAP、CTSK、MMP9)表達升高,且MMT側高于假手術側(P0.01)。結果表明在早期骨關節(jié)炎中,軟骨下骨改建較活躍,骨吸收功能增強,骨形成功能降低,骨吸收與骨形成失去平衡,導致軟骨下骨的微結構發(fā)生改變。
[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.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R684.3
本文編號：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.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R684.3
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