波士頓福塞斯研究所的研究人員確認(rèn),，人類牙齦組織內(nèi)的免疫細(xì)胞在牙周病的過程中起破壞作用。盡管以前研究人員曾懷疑牙周病時骨質(zhì)丟失和免疫細(xì)胞可能有關(guān),，但是福塞斯研究所的研究人員第一次在人類組織標(biāo)本中證明了這一點,。通過這項研究,，福塞斯研究所的研究人員希望能夠找到阻止骨質(zhì)丟失的辦法，從而改善大約八千萬美國牙周病患者的健康狀況,。?
該項研究發(fā)負(fù)責(zé)人是Toshihisa Kawai博士,，這項研究的目的是要弄清在牙周病的情況下針對牙周細(xì)菌的免疫反應(yīng)是起保護(hù)作用還是致病作用。牙周病是一種牙齒及其支持結(jié)構(gòu)的感染性疾病,，這種疾病將會導(dǎo)致組織軟化和骨骼破壞,，從而導(dǎo)致牙齒缺失。Kawai博士及其同事發(fā)現(xiàn)B細(xì)胞能夠通過激活T細(xì)胞而加劇牙周骨質(zhì)的丟失,。該研究小組此前已經(jīng)證明在動物模型中B細(xì)胞和T細(xì)胞能夠?qū)е鹿琴|(zhì)丟失,。Kawai博士說：“我們的研究結(jié)果表明，我們關(guān)于免疫細(xì)胞在牙周病中是有害的這種理論是正確的,。這是一個開創(chuàng)性的發(fā)現(xiàn),，因為這使得人們對牙周病有了一個全新的認(rèn)識，同時還使人們重新認(rèn)識免疫細(xì)胞,。我們希望這項工作能夠幫助我們在將來能夠拯救人類的牙齒,。”??
RANKL是調(diào)節(jié)破骨細(xì)胞的一種重要蛋白，它能夠介導(dǎo)破骨細(xì)胞瘤的發(fā)生,，在這個過程中RANKL主要導(dǎo)致炎癥性骨質(zhì)吸收,。Kawai博士研究的目的之一是在牙周病骨質(zhì)吸收的損傷組織中找到RANKL的細(xì)胞來源，損傷的牙周組織的特點是大量B細(xì)胞和T細(xì)胞的浸潤,，而這兩種細(xì)胞是最重要的免疫淋巴細(xì)胞,。特別是50%-60%的漿細(xì)胞（最終分化為B細(xì)胞）浸潤使得牙周病與其他慢性感染性疾病大不相同。眾所周知B細(xì)胞正常情況下主要制造抗體以保護(hù)肌體免受細(xì)菌感染,。由于牙齦組織中B細(xì)胞的浸潤,，牙周病患者的含有細(xì)菌的牙齦組織中有顯著高水平的抗體。然而,，事實是這樣的,，即使B細(xì)胞產(chǎn)生了抗體以抵御細(xì)菌但是牙周病還是在進(jìn)展，這是一個重要而有趣的問題,。為了回答這個問題Kawai博士的研究小組發(fā)現(xiàn)牙周病患者牙齦組織中的T細(xì)胞和B細(xì)胞能夠表達(dá)RANKL,，這可以導(dǎo)致破骨細(xì)胞發(fā)揮作用，這種破骨作用在實驗室的細(xì)胞培養(yǎng)系統(tǒng)中已經(jīng)得以證明,。因為還沒有發(fā)現(xiàn)在缺失破骨細(xì)胞的情況下細(xì)菌可以侵蝕和吸收骨質(zhì),，所以T細(xì)胞和B細(xì)胞表達(dá)的RANKL被認(rèn)為是激活破骨細(xì)胞的主要因素，從而導(dǎo)致骨質(zhì)丟失而引起牙周病,。
英文原文：
Immune cells put the teeth in gum disease
The body's immune system aids in the progression of devastating gum disease, actually encouraging the cells to eat away bones that support the teeth, researchers in Boston have found.
In an in vitro study of human gingival tissue, researchers discovered that despite a plethora of antibodies present at the site of inflamed gum tissue, a protein called RANKL that is expressed by immune cells is able to override the body's method of defense.
"It's a groundbreaking discovery because it truly gives (us) a new understanding of periodontal disease," said lead author Dr. Toshihisa Kawai, an associate professor at the Forsyth Institute, an oral science research organization.
The study, which will be published in the September issue of the American Journal of Pathology, is the first experiment in human tissue to show that immune cells harm -- not help -- bones around the teeth. The research confirms similar findings from animal research.
However, Kawai does not know if results will hold true for people.
More than one in three Americans over 30, or almost 36 million people, have periodontitis, according to the American Academy of Periodontology. The disease begins mildly as a chronic bacterial infection, then leads to gingivitis, in which plaque inflames the gums. Left untreated, the plaque spreads below the gum line and spurs the growth of toxins, which in turn instigate an inflammatory response in the body -- the hallmark of periodontitis.
The progression of the disease can be gruesome, as the bones supporting the teeth slowly degrade and cause the gums to separate from the teeth. Gum disease is a major cause of tooth loss in Americans.
Yet for decades the exact pathology of periodontitis has remained out of reach for scientists. In recent years researchers have been working to explain why the bones of the jaw continue to break down despite the fact lymphocytes, or immune system white blood cells, are so abundant. These lymphocytes, which include T and B cells, produce hefty amounts of antibodies to act as weapons against the bacteria.
Usually, the immune system responds to bacteria by protecting the body against it. But in the case of periodontal disease, the opposite occurs: Kawai and colleagues found immune cells also produce an "unwanted pathogenic factor" -- the RANKL protein. This protein regulates osteoclasts, or cells that destroy bone.
In the laboratory culture, the RANKL proteins expressed on the immune cells were potent enough to activate the osteoclasts to disintegrate the bone.
Kawai's data suggests RANKL is a key player in bone loss and periodontal disease, said Dr. Denis Kinane, the associate dean for research at Kentucky's University of Louisville School of Dentistry.
"We don't really understand the path of periodontitis, but we're building up pieces up slowly that could be important in the jigsaw," he said.
Understanding RANKL -- and how to suppress it -- could aid doctors in detecting patients who are susceptible to the condition, Kinane said.
"If it's true that RANKL is pivotal in bone loss, it could give us a target," Kinane said. "We're always looking to understand the pathology of the disease and improve diagnosis."
Those particularly at risk for gum disease are smokers and diabetics. Risk factors include tobacco use, stress, genetics, hormonal changes and poor nutrition. Recent studies have also linked periodontitis to heart disease and low-birth-weight babies.
Kawai has now turned his focus on how to prevent immune cells from producing RANKL. In rat models he has been able to interrupt RANKL expression. Kawai hopes to find chemical compounds or other strategies to inhibit the production in diseased tissue.
"Teeth are very important to provide a joyful life. There is a huge demand to prevent periodontal disease," he said.
