波士顿福塞斯研究所的研究人员确认，人类牙龈组织内的免疫细胞在牙周病的过程中起破坏作用。尽管以前研究人员曾怀疑牙周病时骨质丢失和免疫细胞可能有关，但是福塞斯研究所的研究人员第一次在人类组织标本中证明了这一点。通过这项研究，福塞斯研究所的研究人员希望能够找到阻止骨质丢失的办法，从而改善大约八千万美国牙周病患者的健康状况。?
该项研究发负责人是Toshihisa Kawai博士，这项研究的目的是要弄清在牙周病的情况下针对牙周细菌的免疫反应是起保护作用还是致病作用。牙周病是一种牙齿及其支持结构的感染性疾病，这种疾病将会导致组织软化和骨骼破坏，从而导致牙齿缺失。Kawai博士及其同事发现B细胞能够通过激活T细胞而加剧牙周骨质的丢失。该研究小组此前已经证明在动物模型中B细胞和T细胞能够导致骨质丢失。Kawai博士说：“我们的研究结果表明，我们关于免疫细胞在牙周病中是有害的这种理论是正确的。这是一个开创性的发现，因为这使得人们对牙周病有了一个全新的认识，同时还使人们重新认识免疫细胞。我们希望这项工作能够帮助我们在将来能够拯救人类的牙齿。”??
RANKL是调节破骨细胞的一种重要蛋白，它能够介导破骨细胞瘤的发生，在这个过程中RANKL主要导致炎症性骨质吸收。Kawai博士研究的目的之一是在牙周病骨质吸收的损伤组织中找到RANKL的细胞来源，损伤的牙周组织的特点是大量B细胞和T细胞的浸润，而这两种细胞是最重要的免疫淋巴细胞。特别是50%-60%的浆细胞（最终分化为B细胞）浸润使得牙周病与其他慢性感染性疾病大不相同。众所周知B细胞正常情况下主要制造抗体以保护肌体免受细菌感染。由于牙龈组织中B细胞的浸润，牙周病患者的含有细菌的牙龈组织中有显著高水平的抗体。然而，事实是这样的，即使B细胞产生了抗体以抵御细菌但是牙周病还是在进展，这是一个重要而有趣的问题。为了回答这个问题Kawai博士的研究小组发现牙周病患者牙龈组织中的T细胞和B细胞能够表达RANKL，这可以导致破骨细胞发挥作用，这种破骨作用在实验室的细胞培养系统中已经得以证明。因为还没有发现在缺失破骨细胞的情况下细菌可以侵蚀和吸收骨质，所以T细胞和B细胞表达的RANKL被认为是激活破骨细胞的主要因素，从而导致骨质丢失而引起牙周病。
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.
