The most recent study presented in the Arthritis Research & Therapy journal reports, that cells from knee joints of persons with osteoarthritis have an extremely short telomeres. What’s more, it has appeared that the percentage of cells with ultra short telomeres increases with decreasing distance to the most damaged region of the joint. The published research was conducted by the scientists from Denmark.

Telomeres are regions of eukaryotic chromosomes, located at their ends. Each human cell is consisting of 92 telomeres. They play a very important functional role, which is protection against degradation of chromosomes and maintenance of the integrity and stability of the genome. Therefore they protect against cancer development and are related to the process of cell ageing. Protective function of these structures is dependent on many variables – proteins associated with telomeres (TRAF1, TRAF2, Ku86), the level of telomerase activity or telomeres length. It has been proved that the normal chromosome during the duplication should be shortened. Hence the number of cell divisions is limited by a certain number of cycles (Hayflick’s limit). This process is called the end replication problem. Telomeres shorten during each cell division for approximately 50-200 bp. Together with their length loss, the chromosomes become unstable. After critical reduction of the telomeres, the cell is undergoing an apoptosis. If this sequence of events is disturbed and the cell begins to produce telomerase on its own, so that telomeres will continue to regenerate, the cell will gain immortal properties and become the cancer cell. Then, it will not react to external signals but will retain its own metabolic activity. Theoretically, by knocking out telomerase from the cancer cells, it would be possible to stop their uncontrolled division. It appeared, however, that some advanced tumors do not have cell telomerase. There are several single nucleotide polymorphisms, involved in the genetic regulation of the telomeres length in humans. Such places were identified on the chromosomes 14q23.2 and 12q12.22. Their precise functional meaning and impact on the life of the cell is not fully known. Probably they affect the activity of the telomerase, and therefore the length of the telomeres. An association between neoplastic and non-neoplastic diseases (hypertension, coronary artery disease) and the telomeres length or telomerase activity has been proven. Furthermore, assessment of the telomeres length is used as a diagnostic marker for women with breast cancer.

A team of researchers from Denmark used a newly developed technology (Universal single telomere length assay) to specifically look at the telomeres of cells taken from the knee joints of individuals, who have undergone a replacement operation of this joint. The results of the analysis showed that the average cells telomeres length, which were taken from osteoarthritis patients, were significantly shorter. Moreover, it appeared that “ultra short” telomeres were associated with oxidative stress appearing in the case of joints inflammation underlying osteoarthritis. In conclusion, in the cells of knee joints shorter telomeres were found, and their particular shortening was observed in people with more severe course of osteoarthritis in damaged regions of the joint. In addition, their association with senescence was demonstrated. The organism is ageing in biological aspect by no possibility of renewing the joint cartilages. This suggests the coexistence of two processes in osteoarthritis. On the one hand in its course, telomeres shorten with age of the patient, which reduces the ability of cells to divide and on the other hand, telomeres are reduced due to the inflammation, present within the joint. Scientists believe that these processes overlap, but definitely the second one predominates in the pathogenesis of the osteoarthritis. Are telomeres revealing secrets?

Written by: Karolina Kłoda MD, PhD

Source:
1. Maria Harbo, Laila Bendix, Anne-Christine Bay-Jensen, Jesper Graakjaer, Kent Søe, Thomas L Andersen, Per Kjaersgaard-Andersen, Steen Koelvraa, Jean-Marie Delaisse. The distribution pattern of critically short telomeres in human osteoarthritic knees. Arthritis Research & Therapy, 2012; 14 (1): R12 DOI: 10.1186/ar3687
2. ScienceDaily. Retrieved April 17, 2012, from http://www.sciencedaily.com­ /releases/2012/01/120115223324.htm
3. Domański L, Ciechanowicz A, Ciechanowski K, Bińczak-Kuleta A, Kłoda K, Drozd A, Borowiecka E. Analysis of transrenal DNA content and DNA telomeres length in transplanted kidney recipients urine – project funded by MNiSW.
4. http://medtube.net/orthopedics/medical-videos/2640-unusual-bursitis-of-the-knee-video-lecture

Want to know more? Watch on medtube.net: “Unusual Bursitis Of The Knee – Video Lecture”