Wednesday, 4 April 2012

Stem Cell Research Leading To Potential Treatments for Osteoporosis



Figure 1: Left: normal bone, right: osteoporotic bone 
(International Osteoporosis Foundation 2012)
Have you ever imagined that a tiny molecule can possibly be the key to curing osteoporosis, a gene-related condition that affects many people, mainly over the age of 55 (AIHW 2011)? This discovery is vital as around 3.4% of the total population in Australia are affected by osteoporosis, where 81.9% of those patients are women (AIHW 2011). Even though osteoporosis is not a lethal condition, it accounted for 240 deaths caused by major bone fractures and subsequent complications in 2007 (AIHW 2011). 

Many researches were undertaken to identify the underlying causes for this condition. In 2010, Professor Stuart H. Ralston conducted a study to identify genes that potentially lead to osteoporosis. His findings supported the hereditary nature of osteoporosis, as identified by previous studies (Huang et al. 2006). In additional to the genetic aspect that contributes to osteoporosis, the fact that adult stem cells found in the bone marrow, stop migration to the bones as aging progresses (Guan et al. 2012) is also another important factor to osteoporosis. The lack of osteoblasts produced from adult stem cells decreases the amount of bone formation. However, osteoclasts continue to break down bones to provide calcium to the blood stream (Jacob-Kosmin, D 2011). As a result, the bone-mass-density decreases which in turn increases the chance of bone fractures.
Figure 2: Hematopoietic and stromal stem cell differentiation (National Institute of Health resource for stem cell research 2012)

Earlier this year, a group of scientists from the UC Davis Health System, investigated for a possible treatment for osteoporosis via the manipulation of adult stem cells using chemicals. They created a molecule that consisted of 2 ends, the LLP2A end and the alendronate end (Guan et al. 2012). LLP2A is a ligand that sticks to the α4β1 receptor found on the surface of stem cells (Guan et al. 2012), leading to their activation. Alendronate, on the other hand, is a drug that is widely used to prevent bone resorption by inhibiting osteoclast activity (Guan et al. 2012). Overall, this molecule should act as a mediator to drag the stem cells to bones. This will allow more stem cells to be transformed to osteoblasts and make bones, which in turn increase the bone density and strength.

Figure 3: Synthetic scheme of LLP2A-Ale (Guan et al. 2012)
Their experiment involved injecting a controlled amount of LLP2A-Alendronate and LLP2A into two groups of osteoporotic mice respectively. The group that received the LLP2A-alendronate molecule shows an increase in bone density in the thighbone 12 weeks following injections compare to the control group. However, the group that received LLP2A did not show any changes in bone mass density (Guan et al. 2012), but the ability of stem cells to find and stick to bones increased. These results seem to suggest an increased homing ability for stem cells to bones after the activation of the α4β1 receptor, but it also suggests that alendronate is essential to the cure of osteoporosis (Guan et al. 2012).

Professor Jan Nolta, one of the researcher, finds the results “very promising”, especially in view of the potential “(translation) into human therapy” (UC Davis Health System 2012). Not only can this treatment potentially cure osteoporosis, this amazing discovery may be the missing piece to the puzzle of treating other medical conditions that require bone-regrowth in the future (UC Davis Health System 2012).


Bibliography:

Australian Institute of Health and Welfare 2011, A snapshot of osteoporosis in Australia 2011, Arthritis series no. 15. Cat. No. PHE 137, Australian Institute of Health and Welfare, Canberra

Guan, M, Yao, W, Liu, R, Lam, K, Nolta, J, Jia, J, Panganiban, B, Meng, L, Zhou, P, Shahnazari, M, Ritchie, R & Lane, N 2012, “Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass”, Nature Medicine, vol. 18, no. 3, pp. 456-463

Huang, Q & Kung A, “Genetics of osteoporosis”, Molecular Genetics and Metabolism, vol. 88, Issue 4, pp. 295-306

International Osteoporosis Foundation 2012, What is Osteoporosis, International Osteoporosis Foundation, viewed 10th March 2012, <http://www.iofbonehealth.org/patients-public/about-osteoporosis/what-is-osteoporosis.html >

Jacobs-Kosmin, D 2011, Osteoporosis, Medscape Reference, viewed 17th March 2012, <http://emedicine.medscape.com/article/330598-overview#a0104>.

National Institute of Health resource for stem cell research 2012, Stem Cell Information, National Institute of Health, United States, viewed on 7th March 2012,  <http://stemcells.nih.gov/info/basics/basics4.asp>

Ralston, S 2010, “Genetics of osteoporosis”, Annals of the New York Academy of Sciences, vol. 1192, Issue 1, pp. 181-189

UC Davis Health System 2012, UC Davis investigators develop method of directing stem cells to increase bone formation and bone strength, UC Regents, Sacramento, viewed on 12th March 2012, <http://www.ucdmc.ucdavis.edu/publish/news/stemcellresearch/6195>.


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