The Alteration Of Subchondral Bone Microstructure And The Expression Of Bone Remodeling Related Genes In Initial Of Osteoarthritis

Osteoarthritis is a common disease that can cause severe pain and dysfunction in any joint,including the temporomandibular joint(TMJ).Temporomandibular joint disorder is a common disease,frequently-occurring disease in the field of stomatology,with a morbidity of 11.4%-58.0%,usually affecting people from the age of 30.2 to that of 39.6,and having almost 2.3 times more female patients than male ones.The morbidity increases along with the age,e.g.,eighty out of one hundred patients older than 60 year old once suffered from TMJ osteoarthritis(TMJOA),featuring pain from the joints and difficulty in opening mouth,with their life being harmed greatly.TMJOA is an important subtype in the classification of temporomandibular disorders(TMDs),of which the main pathological change is the degeneration of the joints' cartilage,accompanied by the sclerosis of the subchondral bone and the advent of redundant bone.It has been proved,by lots of experiments,that the degeneration of the joints' cartilage could be put off through cytokines-regulated subchondral bone reconstruction.For the time being,most treatments for the TMJOA comprise non-surgery methods,e.g.,physical therapies,wearing a pair occlusal pads,the administration of non-steroids,and the injection of lubricating liquid or steroids into the articular cavity.The aims are to relieve symptoms,stop the exacerbation of temporomandibular joint disorder,and recover their functions.Recently,much progress has been made on the research of TMJOA,while the etiology,pathology,and the development still need further exploring and discussing.Former researches focused more on the role of the alterations of the joints' cartilage in the TMJOA,less on that of the subchondral bone.Lately it has been assumed that the alterations of the subchondral bone may be prior to the degeneration of the joints' cartilage.Both the subchondral bone and the joints' cartilage constitute parts of a same whole joint,leaving neither one being ignored,while the testing indicators for their changes differ from each other,and that is why no proved theories have been made as to the question that which one initiates the progression.Although the conclusion that the alterations of the subchondral bone precedes the degeneration of the joints' cartilage remains to be proved,but there is one point for sure that the alterations of the subchondral bone is an indispensable part in the development of osteoarthritis.Former researches mainly focused on the etiology and characteristics of the breaking joints' cartilage,and seldom on the features of the changing subchondral bone.There are more and more researches showing that the subchondral bone holds an important position in the development of osteoarthritis,which sets a new orientation for studying and treating osteoarthritis.The laboratory I worked for prepared to erect an animal model of studying the initial stage of osteoarthritis on SD rats,where radiography and histopathological technics were adopted to localize the micro-changes of the subchondral bone,to learn more about the alterations of both the subchondral bone and the joints' cartilage,and to characterize the changing genes by detecting the different expressions of those relative genes correlating to bone reconstruction,in the initial stage of osteoarthritis.The aim of this experiment was to find out more evidences for early diagnosing of osteoarthritis by detecting the micro-changes of the subchondral bone,and curing osteoarthritis by interfering with the bone reconstruction of the subchondral bone.The main research results and conclusions are listed below:1?The animal model of initial stage of osteoarthritis was constructed successfully through the MMT surgery.After three weeks of the surgery,evidences like the surface of the joints' cartilage being not damaged but covered by grey-white with less brightness,as well as the controlled side being normal,indicated that the medial meniscal tear(MMT)surgery could initiate the joints' degeneration.2?The Micro-CT was adopted to reconstructed and analyses the subchondral bone of animals in the initial stage three-dimensionally.On the MMT side,the volume percentage of the subchondral trabeculae(BV/TV)decreased,the thickness of trabeculae(Tb.Th)decreased,the connection density of trabeculae(Conn.D)decreased(P<0.05),the trabecular space(Tb.Sp)increased(P<0.05),and the trabecular number(Tb.N)decreased(P> 0.05).By inspecting the tissue section,we fount sparsely distributed trabeculae,but barely found degenerated cartilage,which indicated that the volume of the subchondral bone slightly decreased in the initial stage of osteoarthritis.3?Relative genes relating to the subchondral bone reconstruction were tested.The results of rt-PCR showed that,the osteogenesis relevant genes(alkaline phosphatase,ALP;runt-related gene 2,RUNX2;osteocalcin,OCN)were greatly expressed three weeks after the surgery,while genes on the MMT side expressed less than the controlled side(P<0.05),which indicated that osteogenesis decreased.The osteoclastic genes(tartrate-resistant acid phosphatase,TRAP;Cathepsin k,CTSK;matrix metalloproteinase-9,MMP9)expressed increasingly,and more on the MMT side than the control(P<001).These results indicated that the subchondral bone reconstructed itself actively,then the homeostasis of bone absorbing and bone formation was no longer kept when the former overwhelmed the latter,finally causing the microstructure of the subchondral bone's being altered.