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Author and Reporter: Anamika Sarkar, Ph.D and Ritu Saxena, Ph.D.

 Cartilage is the tissue lining of the joints and acts as a cushion between the joints. Osteoarthritis, a disease accompanied by severe pain and limitations of functions, is the result of degeneration of cartilage. Currently, such conditions of patients are considered irreversible and treatment options are mainly based on pain management and joint replacement therapy.

Some of these procedures are –  Autologous Chondrocyte Implantation (ACI), Osteochondral Allograft Transplantation, Meniscal Transplantation. In these procedures, healthy cartilage (or meniscus in case of Meniscal Transplantation) are taken either from the patients or deceased donors and transplanted in the damaged joints for cartilage repair. (Please see information regarding cartilage repair, cartilage supplement in sources below).

Harnessing use of regenerative powers of stem cells have been recognized as alternative methods of treatments. Stem cells are the cells that have the capacity to develop into different cell types. They can continue to renew themselves with cell division without being differentiated.  Moreover, with the right stimulus they can also be induced to differentiate into specialized cell types. Thus, with discovery and understanding of right stimuli and its signaling processes, stem cells can serve as a powerful candidate for repair of damaged tissues and organs.

Since, stem cells are precursor of many differentiated cell types, a lot of research is needed to determine the right conditions to direct the stem cell differentiation into the desired cell type for the purpose of treatment. Attempts have been made in the area of regenerative medicine for cartilage regeneration using stem cells. Kafienah et al (2007) bioengineered a three-dimensional cartilage using adult stem cells from the bone marrow of osteoarthritis patients. Although, this method could thus be used for repairing cartilage lesions, however, it needs to be implanted into the joint adding challenges to the development of therapy.

A very interesting study published in the recent issue of the journal Science (Johnson et. al., A Stem Cell-Based Approach to Cartilage Repair, Science, 336, p717,2012) described breakthrough discovery – a small molecule, Kartogenin (KGN), has the capability of promoting chondrocytes (cells which make healthy cartilage) differentiation.

The authors, Johnson et al. showed their finding of KGN as a stimulus for stem cell differentiation to chondrocytes in a systematic fashion. They used high throughput screening of images from 5 primary human stem cells derived from bone marrow in their in-vitro studies. Their results show when cells were treated with 100nM of KGN, they show regeneration of cartilage forming chondrocytes. They supported their finding in animal model using mice model by inducing Osteoarthritis and then treating them with KGN.

In order to make sure that KGN has a direct effect on the signaling of chondrocytes, Johnson et. al., showed activation of some of the key signaling components in the KGN stimulated chondrocytes pathway, using in-vitro studies. They showed that upon activation of cells with KGN, CBFb (core-binding factor β subunit)  translocates into the nucleus and activates signaling components of  RUNX (one of the runt-related transcription factor family member), leaving behind free cytoplasmic binding partner FLNA (Flaming A). They also show strong correlation between CBFb and regeneration of chrondocytes.

Stem cell therapy has uncounted potential for giving better life to patients with complex, chronic diseases.  Johnson et al’s, discovery of a small molecule, KGN, with further research in animal and human population, could lead to the development of an effective stem cell based treatment of Osteoarthritis. A possibility of such a drug can be seen as a lifestyle changing drug in patients who have very limited options of treatments today.

Sources:

Johnson et al article:  http://www.ncbi.nlm.nih.gov/pubmed/22491093

Arthritis information: http://orthopedics.about.com/cs/arthritis/a/arthritis.htm, h

http://www.cirm.ca.gov/node/2082

Stem cells: http://www.stemcellresources.org/pdf/uw_rm.pdf

http://stemcells.nih.gov/staticresources/info/scireport/PDFs/Regenerative_Medicine_2006.pdf

Kafienah et al article: http://www.ncbi.nlm.nih.gov/pubmed/17195220

Previous post in awesome capital on the paper by Johnson et. al. :  http://www.awesomecapital.com/1/post/2012/04/novartis-anti-arthritis-compound-spurs-cartilage-growth-from-stem-cells.html

Information about cartilage repair : http://www.jointpain.md/Procedures/CartilageTransplant.aspx

Cartilage Supplement in iHealth directory:http://www.ihealthdirectory.com/cartilage-regeneration-supplements/

Information about modern cartilage repair treatments offered at Brigham and Women Hospital: http://www.brighamandwomens.org/Departments_and_Services/orthopedics/services/CartilageRepair/default.aspx