Osteoarthritis: some hints

sources: Orthopaedic Research Society and PR Newswire

According to Wikipedia, Osteoarthritis (OA) is a type of joint disease that results from breakdown of joint cartilage and underlying bone. The most common symptoms are joint pain and stiffness. Initially, symptoms may occur only following exercise, but over time may become constant. Other symptoms may include joint swelling, decreased range of motion, and when the back is affected weakness or numbness of the arms and legs. The most commonly involved joints are those near the ends of the fingers, at the base of the thumb, neck, lower back, knee, and hips. Joints on one side of the body are often more affected than those on the other. Usually the symptoms come on over years. It can affect work and normal daily activities. Unlike other types of arthritis, only the joints are typically affected.

OA affects the entire joint, progressively destroying the articular cartilage, including damage to the bone. Patients suffering from OA have decreased mobility as the disease progresses, eventually requiring a joint replacement since cartilage does not heal or regenerate. According to a 2010 Cleveland Clinic study, OA is the most prevalent form of arthritis in the United States, affecting more than 70% of adults between 55 and 78 years of age (that is, millions of people).

“My father was in major pain from his osteoarthritis,” explains Riccardo Gottardi, a scientist at the University of Pittsburgh supported by a Ri.MED Foundation fellowship.  “He was in so much pain that he had to undergo a double hip replacement followed by a knee replacement soon afterwards. I could see the debilitating and disabling effects the disease had on him, as he was restricted in his mobility and never fully recovered even after surgery. This was very different from the person that I knew, who had always been active and never shied away from long hours of work in his life – he just could not do it anymore.“

For scientists like Gottardi, a key obstacle in understanding the mechanisms of osteoarthritis and finding drugs that could heal cartilage, is that cartilage does not exist separately from the rest of the body. Cartilage interacts with other tissues of the joint, especially with bone. Bone and cartilage strongly influence each other and this needs to be taken into account when developing new drugs and therapies.

Gottardi and a team of researchers at the Center for Cellular and Molecular Engineering, led by Dr. Rocky Tuan, have developed a new generation system to produce engineered cartilage, bone and vasculature, organized in the same manner as they are found in the human joint.  This system is able to produce a high number of identical composite tissues starting from human cells. The team will use this system to study the interactions of cartilage with vascularized bone to identify potential treatments for osteoarthritis. The team’s research has two main objectives: to help understand how cartilage interacts with the other joint tissues, especially bone; and to help develop new effective treatments that could stop or even reverse the disease.  Their patent pending system is the first of its kind, and offers a number of advantages including the use of human cells that replicate native tissues. This system more closely matches the effects on humans than standard animal testing could achieve.

The team of scientists is further developing their system to produce tissues composed of more and different cell types that could better replicate the human joint. They have also started a number of collaborations with other research groups and companies that are interested in using the system to investigate other joint diseases and to test their product. “After seeing what my father went through,” says Gottardi, “I decided that I did not want to just watch by working on diagnostics, but rather, I wanted to be able to do something about osteoarthritis and contribute to the improvement of current treatment options.“

Gottardi’s work was recently presented at the Annual Meeting of the Orthopaedic Research Society. Founded in 1954, the Orthopaedic Research Society strives to be the world’s leading forum for the dissemination of new musculoskeletal research findings.

breakthrough could prevent Hip Implant Replacement

source: copy-pasted from this website

World-leading researchers from the University of Sheffield have identified a molecule which can be targeted to reduce the loosening of hip implants by preventing toxic metal entering into bone cells.

Hip implants rely on the normal functioning of bone cells to achieve fixation of the implant with the bone. However, small metal particles released from hip implants, due to friction between the moving surfaces, have been shown to be toxic to the surrounding bone cells. This causes the implant to loosen in the bone and often leads to patients requiring second surgery to replace the failed implant.

Using X-ray light from the Diamond Light Source (the UK’s synchrotron science facility at Harwell Science and Innovation Campus, Oxfordshire), researchers were able to map the locations of metals inside bone cells. The findings, published in the Journal of Orthopaedic Research, show that the location of the metals that are released from implants is different inside bone building and bone destroying cells.

Dr Alison Gartland, Senior Lecture from the University’s Academic Unit of Bone Biology, said: “The fact that we found metal ions in different places within the two types of bone cells suggest that they get into the cells by separate ways. When investigating how the metals entered bone cells we found that when we blocked a molecule called the P2X7 receptor using a specific drug, the entry of metals into the bone cells was reduced. These results are really exciting because, if we can prevent the entry of the metal into these cells, we can hopefully prevent the metal joint from failing.”

Over the last decade, it is estimated that nearly half a million hips have been replaced in England and Wales as a result of osteoarthritis. Osteoarthritis is the most common joint disorder in adults, affecting nearly eight million people in the UK alone. Surgical replacement of the joint using artificial metal implants is the most effective way to restore activity and reduce pain and disability in osteoarthritis sufferers. The research was funded by the National Institute for Health Research (NIHR) and in collaboration with Diamond Light Source.