Cause of Osteoarthritis Discovered

The fundamental cause of osteoarthritis, a puzzle that had thus far proven elusive to resolve, has been identified by Korean researchers.

A research team led by life science professor Chun Jang-soo at the Gwangju Institute of Science and Technology has resolved the puzzle of osteoarthritis with support from the Leading Research Center Assistance Program, conducted by the Ministry of Education, Science and Technology(Ahn Byung-man, Minister), and the Korea Research Foundation (Park Chan-mo, Chairman). The team discovered that the HIF- gene regulates diverse factors that cause degeneration of cartilage cells and spur the disease's development.

Hypoxia-inducible factor- is a protein that was known first as a transcription factor whose protein volume increases due to hypoxia. In this study, this protein has been found, apart from previously known functions, to regulate the emergence of diverse genes that are involved in osteoarthritis.

Osteoarthritis is characterized by cartilage tissue that gradually wears down and fails to recover due to inherent factors, including aging and heredity, or mechanical factors, such as damage or obesity. According to studies, eight out of 10 elderly citizens aged 65 or older in Korea suffer from the disease.

However, the cause and treatment of the condition had not been discovered thus far.

HIF- is excessively expressed in cartilage tissue due to DMM (ligament surgery), as well as mechanical stress resulting from the injection of 'collagenase,' or inflammatory cytokine (IL-, etc). HIF- induces osteoarthritis by regulating the emergence of factors that cause cartilage degeneration as transcription factors, or factors including MMP1, 3, 9, 12, and 13 and ADAMTS4, which dissolve cartilage matrix, as well as the expression of genes that cause inflammation such as iNOS and COX-2.

MMP (matrix metalloproteinase)
This is an enzyme protein that dissolves extracellular matrix; more than 20 types of this protein exist. If these enzymes are activated in the course of cartilage destruction, cartilage matrix molecules are dissolved, inducing regenerative arthritis.
ADAMTS (matrix metalloproteinase)
Among the extracellular matrix that comprises cartilage, ADAMTS(matrix metalloproteinase) is an enzyme that dissolves sulfate proteoglycan; diverse types of the enzyme exist. Notably, ADAMTS-4 and ADAMTS-5 are known to be involved in osteoarthritis.

The researchers also found that if HIF- is artificially generated in cartilage of mice or rabbits, it induces severe osteoarthritis; whereas if HIF- is lacking, osteoarthritis does not occur. Thus, the researchers have opened up the possibility for both prevention and treatment of the condition.

The photo on the left shows the development of osteoarthritis in a genetically modified mouse in which HIF- is excessively expressed in cartilage; the photo on the right shows the suppression of osteoarthritis in a genetically modified mouse, which lacks HIF-.

Explaining the significance of his study

The study will be published as a notable paper in the latest issue of Nature Medicine, the academic journal on basic biomedical science.

Lim Dong-Wook
duim at kofac.or.kr

[June 15, 2010]

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Source - ScienceTimes