How stiff are your joints?

Atomic force microscopy (AFM) can detect osteoarthritis several months before conventional morphology-based diagnostic techniques, say researchers from Germany, Switzerland, and Italy [Stolz, et al., Nat. Nanotechnol. (2009), doi: 10.1038/nnano.2008.410].

Osteoarthritis is a degenerative disease that starts at the molecular scale and progresses to the macroscale in cartilage, a load-bearing tissue located in bone joints. There is currently no cure for the disease and early detection and the ability to monitor the disease's progression would be a major step forwards.

Cartilage tissue is made up of a network of molecules called collagen and proteoglycans. “In aging and osteoarthritis the soft sugar molecules, which are the proteoglycans, change their structure, but the hard collagen fibrils are apparently not affected at the early stages ”, explains Michael Stolz of the University of Basel in Switzerland. “Therefore, in order to detect early changes of osteoarthritis, the diagnostic tool needs to be sensitive to the changes in the proteoglycan moiety. Such analysis can be done by biochemical and/or histological analysis, but such methods require biopsies and, therefore, are destructive. Even a very small biopsy taken from the hip- or knee joint would be a seeding point for osteoarthritis.”

Another way of detecting cartilage deterioration is by measuring the tissue's stiffness. However, current techniques only work at the micron scale, by which time the disease has already progressed by around five months. In this new work, the team uses an indentation-type atomic force microscope (IT-AFM) to measure stiffness on the nanoscale and hence detect the disease at a much earlier stage. Here, an AFM tip is pressed into the material and the response is directly measured.

When the researchers studied mice with the phenotype for osteoarthritis, they detected differences in stiffness of cartilage tissue as early as one month into the mouse's lifetime when compared with that of normal mice. Tests on humans undergoing hip replacements also indicated a marked change in nanoscale stiffness, even in the early stages of osteoarthritis.

The next step is to develop a user-friendly in situ indentation type-AFM for clinics. In the future the team also hopes to study tumors, but there are some major questions to be answered first. “It is not so clear how a change in the mechanical properties of breast tissue in a tumor relates to its functional role in the body. This leads to the difficulty of how to interpret measured changes. Moreover, cancerous tissue is much more complex compared to cartilage”, says Stolz.