In a study to be published online Nov. 6 in Nature Medicine, investigators at the Stanford University School of Medicine have demonstrated that the development of osteoarthritis is in great part driven by low-grade inflammatory processes. This is in contradiction with the prevailing view attributing the condition to a lifetime of wear and tear on long-suffering joints.
But Robinson’s paper suggests a different form of understanding the disease. Its findings offer hope that by targeting the inflammatory processes that occur early on in the development of osteoarthritis? well before it progresses to the extent that symptoms appear? the condition might someday be preventable.
A young woman suffers from a rare condition which means she has already had to have both knees and hips replaced at just 27. She believes it was triggered by a simple viral infection she suffered in her first year at school. She recalls being sent home, but 24 hours later she couldn’t move any part of her body and didn’t return to school for 18 months. She said: ‘It just came on completely randomly and when I tried to move, …
Robinson is an associate professor of immunology and rheumatology at Stanford and a staff physician with the Veterans Affairs Palo Alto Health Care System. The first authorship of the study is shared by research associate Qian Wang, MD, PhD, and Andrew Rozelle, MD, a former Stanford rheumatology fellow now at the Palo Alto Medical Foundation.
Osteoarthritis is the most frequent joint disease, afflicting some 27 million people around the United States alone. It is characterized by breakdown of cartilage, most frequently in the knees, hips, fingers and spine. Drugs commonly used to treat osteoarthritis, such as acetaminophen and ibuprofen, relieve pain but don’t slow the disease’s progression.
It has long been known that osteoarthritic joint tissues host a heightened number of migratory inflammatory cells and of a number of the substances these cells secrete? ‘not nearly as much as in the event of rheumatoid arthritis. This is clearly an autoimmune disease, but enough to make us wonder if inflammation is also an important player in osteoarthritis as well,’ Robinson said. His team’s observation of increased numbers of certain specialized inflammatory proteins early in the progression of osteoarthritis, before it becomes symptomatic, suggested that inflammation might be a driver, instead of a secondary consequence, of the disease.
The new study showed that, indeed, initial damage to the joint sets in motion a string of molecular events that escalates into an attack upon the damaged joint by one of the fund’s key defense systems against bacterial and viral infections, the so-called complement system. This sequence of events involves activation of a chain reaction called the ‘complement cascade,’ and begins early in the development of osteoarthritis.
The complement system consists of an orchestra of proteins present in blood. Upon activation of the complement cascade? typically, in response to the occurrence of bacterial or viral infection? these proteins participate in a complex interplay, variously enhancing or inhibiting one another’s actions at certain points and culminating in the activation of a protein cluster called the MAC (for ‘membrane attack complex’). The MAC helps to remove the body of infections by punching holes in the membranes of bacterial or virally infected human cells.
An early clue regarding the complement system’s key role in osteoarthritis came when Robinson and his colleagues, employing advanced lab techniques, compared the levels of large amounts of proteins present in the joint fluid taken from osteoarthritis patients with levels present in fluid from healthy individuals. They found that the patients’ tissues had a relative overabundance of proteins that serve as accelerators in the complement cascade, along with a shortage of proteins that act as brakes.
Robinson’s group also examined the activity level of genes (which are recipes for proteins) in joint-lining tissues of osteoarthritic versus healthy subjects, and observed a similar result: more expression of genes encoding complement-activating and related inflammatory proteins, and less expression of genes encoding complement-and inflammation-inhibiting ones, in the osteoarthritic patients’ joint tissues.
To further explore the complement system’s role in osteoarthritis, the researchers induced the equivalent of meniscal tears or removal in mice who (like humans) are far more prone to getting osteoarthritis in joints that have suffered such damage. The procedure was performed on normal mice and on three separate strains of bioengineered lab mice, each strain missing a different protein part of the complement system. In two cases, the missing protein was one that normally acts as an accelerator within the complement cascade, and in the developing case one that serves as a brake.
The normal mice developed osteoarthritis as expected. But in comparison with these mice, the two strains of bioengineered mice lacking a complement-cascade-accelerating protein developed less-severe arthritis, while the mice lacking the complement-inhibiting protein got worse, faster. Thus, mice with impaired complement activation were protected from the development of osteoarthritis in response to meniscal damage.
Next, Robinson’s team asked how complement was causing osteoarthritis. Further experiments in mice and with human tissue showed that the MAC, the heavy artillery of the complement system, was damaging joint-tissue cells, but not by punching holes in them. Instead, it was binding to cartilage-producing cells in these tissues and causing them to secrete, on their own, still more complement-component proteins as well as other inflammatory chemicals, and other specialized proteins, or enzymes, that chew up the matrix of cartilage occupying the spaces between cells. They demonstrated that breakdown products of cartilage destruction, including one called fibromodulin, can directly activate the complement system, fostering a continuing cycle of joint-tissue damage.
Finally, the investigators showed that all these insults inflicted by the complement system? measured by microscopic examination of mouse joints? were mirrored by functional impairment. Bioengineered mice lacking a key complement-component protein, without which the complement system fails to activate, maintained their ability to walk normally, while normal mice developed a hindered gait due to severe osteoarthritis following meniscal injury.
Drugs that target the complement system may someday prove useful in preventing the onset of osteoarthritis in people who’ve suffered joint injuries, Robinson said, though he warned that this system is so crucial to our defense against microbial infection that systemic delivery of complement inhibitors would probably not be safe. But it may be that a short period of local administration of a complement inhibitor might provide benefit to patients developing osteoarthritis, while minimizing their risk for the development of infections.
What are the symptoms of arthritis?What are the symptoms of arthritis
Hope these links help..they have wealth of simple-to-understand information…and I hope you or your loved one feel better: http://www.webmd.com/osteoarthritis/guide/understanding-arthritis-symptoms http://arthritis-symptom.com/ Signs and symptoms of the most common rheumatoid arthritis may include: Joint pain Joint swelling Joints that are tender to the touch Red and puffy hands Firm bumps of tissue under the skin on your arms (rheumatoid nodules) Fatigue Morning stiffness that lasts at least 30 minutes Fever Weight loss Signs and symptoms appear in smaller joints first Rheumatoid arthritis usually causes problems in several joints at the same time. Early rheumatoid arthritis tends to affect your smaller joints first — the joints in your wrists, hands, ankles and feet. As the disease progresses, your shoulders, elbows, knees, hips, jaw and neck can also become involved. Signs and symptoms of a rheumatoid arthritis flare Rheumatoid arthritis signs and symptoms may vary in severity and may even come and go. Periods of increased disease activity — called flare-ups or flares — alternate with periods of relative remission, during which the swelling, pain, difficulty sleeping, and weakness fade or disappear.
The symptoms you experience will depend greatly on the type of arthritis or rheumatism you are suffering with. However, the following symptoms may indicate that you have arthritis or rheumatism: Swelling in one or more joints. Stiffness around the joints. Joints that look red and can be warm to the touch. Constant or recurring pain in a joint that has no obvious cause. Sudden difficulty in moving or using a joint. Any joint in the body can be affected by arthritis and rheumatism. However, the knees, fingers and hips are the joints most commonly affected.If you have rheumatoid arthritis you may also experience a mild fever and loss of appetite or energy. Symptoms of arthritis tend to be worse in the morning and sometimes in cold, damp weather. When the affected joints are moved you may hear a click or crack.