早期骨關(guān)節(jié)炎軟骨下骨微結(jié)構(gòu)改變和骨改建相關(guān)基因表達(dá)研究
發(fā)布時(shí)間：2019-02-22 12:03
【摘要】：骨關(guān)節(jié)炎是一種常見的疾病,在全身各關(guān)節(jié)均可發(fā)生,可引起嚴(yán)重的疼痛和功能障礙,包括顳下頜關(guān)節(jié)。顳下頜關(guān)節(jié)紊亂是口腔醫(yī)學(xué)領(lǐng)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(guò)TMJOA的癥狀,其臨床癥狀主要為關(guān)節(jié)區(qū)疼痛、關(guān)節(jié)運(yùn)動(dòng)功能障礙、關(guān)節(jié)彈響及雜音等,患者的身體健康和生活質(zhì)量受到嚴(yán)重影響。顳下頜關(guān)節(jié)骨關(guān)節(jié)炎是顳下頜關(guān)節(jié)紊亂的一種重要的類型,其主要的病理改變是關(guān)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(shí)驗(yàn)結(jié)果表明,通過(guò)細(xì)胞因子調(diào)控軟骨下骨的骨重塑能夠延緩關(guān)節(jié)軟骨的退化。目前臨床治療顳下頜關(guān)節(jié)骨關(guān)節(jié)炎的方式主要包括非手術(shù)方案,如物理療法,佩戴咬合墊,非甾體抗炎藥的使用,和關(guān)節(jié)注射潤(rùn)滑液或皮質(zhì)類固醇等。治療的目的旨在緩解癥狀,阻止顳下頜關(guān)節(jié)疾病進(jìn)展和恢復(fù)顳下頜關(guān)節(jié)的功能。近些年來(lái),國(guó)內(nèi)外在OA和TMJOA的研究上取得了重大進(jìn)展,但其病因、發(fā)展過(guò)程,以及發(fā)病機(jī)制仍需進(jìn)一步探討。以往研究對(duì)關(guān)節(jié)軟骨的改變?cè)贠A中的作用進(jìn)行了大量的研究,對(duì)軟骨下骨的研究較少。近來(lái)有學(xué)者提出,軟骨下骨在骨關(guān)節(jié)炎中可能早于關(guān)節(jié)軟骨的退變。軟骨下骨與關(guān)節(jié)軟骨作為關(guān)節(jié)整體的一部分,在解剖結(jié)構(gòu)上相互依存,而關(guān)節(jié)軟骨的破壞與軟骨下骨的改變檢測(cè)指標(biāo)靈敏度不同,很難說(shuō)清兩者之間誰(shuí)為始發(fā)因素。盡管軟骨下骨的改變?cè)贠A中是否早于關(guān)節(jié)軟骨的退變尚未得到明確的結(jié)論,但可以肯定的是,軟骨下骨在骨關(guān)節(jié)炎的病理變化過(guò)程中必然發(fā)生改變。以往的研究主要集中在關(guān)節(jié)軟骨的破壞及機(jī)制上,對(duì)軟骨下骨在早期骨關(guān)節(jié)炎中的改變研究較少。越來(lái)越多的研究表明軟骨下骨在骨關(guān)節(jié)炎的發(fā)生發(fā)展中有重要作用,為探索骨關(guān)節(jié)炎的研究和治療提供了新的方向。綜上所述,本實(shí)驗(yàn)擬先建立SD大鼠早期骨關(guān)節(jié)炎實(shí)驗(yàn)動(dòng)物模型,通過(guò)影像學(xué)和組織病理學(xué)技術(shù)研究軟骨下骨在早期骨關(guān)節(jié)炎中的微結(jié)構(gòu)改變,了解軟骨下骨和關(guān)節(jié)軟骨在早期骨關(guān)節(jié)炎中的改變,最后通過(guò)檢測(cè)骨改建相關(guān)基因在早期骨關(guān)節(jié)炎中的表達(dá)差異,了解骨形成與骨吸收相關(guān)基因在早期骨關(guān)節(jié)炎軟骨下骨的表達(dá)變化。為檢測(cè)軟骨下骨的微結(jié)構(gòu)改變?cè)\斷早期骨關(guān)節(jié)炎和通過(guò)干擾軟骨下骨的骨改建過(guò)程治療骨關(guān)節(jié)炎提供一定的實(shí)驗(yàn)依據(jù)。本實(shí)驗(yàn)的主要研究結(jié)果和結(jié)論如下:1、通過(guò)MMT手術(shù)成功制作早期骨關(guān)節(jié)炎實(shí)驗(yàn)動(dòng)物模型。術(shù)后3周,MMT側(cè)關(guān)節(jié)軟骨面無(wú)破損,灰白,失去原有光澤,假手術(shù)側(cè)關(guān)節(jié)面正常。表明MMT術(shù)能造成關(guān)節(jié)的退變。2、利用Micro-CT影像學(xué)手段對(duì)實(shí)驗(yàn)動(dòng)物早期骨關(guān)節(jié)炎軟骨下骨進(jìn)行三維重建、分析,MMT側(cè)軟骨下骨小梁骨的骨體積分?jǐn)?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(shù)后3周組織病理學(xué)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(guān)節(jié)炎中軟骨下骨量輕微降低。3、軟骨下骨改建相關(guān)基因檢測(cè),Rt-PCR結(jié)果顯示,術(shù)后3周軟骨下骨的成骨細(xì)胞相關(guān)基因(ALP、RUNX2、OCN)大量表達(dá),MMT側(cè)小于假手術(shù)側(cè)(P0.05),表明骨形成降低。破骨細(xì)胞相關(guān)基因(TRAP、CTSK、MMP9)表達(dá)升高,且MMT側(cè)高于假手術(shù)側(cè)(P0.01)。結(jié)果表明在早期骨關(guān)節(jié)炎中,軟骨下骨改建較活躍,骨吸收功能增強(qiáng),骨形成功能降低,骨吸收與骨形成失去平衡,導(dǎo)致軟骨下骨的微結(jié)構(gòu)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(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R684.3
本文編號(hào)：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(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R684.3
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