Navigation Links
Genetic disorder sheds light on enzyme's role in bone metabolism
Date:11/4/2008

Pycnodysostosis, a condition from which the painter Henri de Toulouse-Lautrec suffered, is a genetic disease characterized by short stature. This rare disease, surprisingly, provides a window into how joints are destroyed by arthritis. It is caused by deficiency of an enzyme known as cathepsin K which hampers osteoclasts (the cells that break down bone in bone modeling and repair), leading to poor bone resorption and dense, brittle bones.

Cathepsin K's role in bone metabolism has largely been studied using mouse models, but a new study examines the enzyme's role in bone resorption in a human patient and shows that it is not required to break down bone. The study was published in the November issue of Arthritis & Rheumatism (http://www3.interscience.wiley.com/journal/76509746/home).

Led by Professor Yrj T. Konttinen of Helsinki University Central Hospital in Helskinki, Finland , the study involved a 55-year-old female patient with pycnodysostosis who also developed psoriatic arthritis. Since the patient lacked cathepsin K due to her condition, researchers hypothesized that this would protect her from the bone erosions in the hands and feet normally seen in psoriatic arthritis. However, she did in fact develop extensive erosions and destructive bone changes in her hands. Blood analysis was conducted to examine the proteinases (enzymes that break down proteins) responsible for bone degradation as well as the cellular mechanisms of bone resorption.

The analyses showed that the osteoclasts formed by the patient lacked cathepsin K, which was expected. Surprisingly, however, this deficiency did not prevent cells from resorbing bone, although the resorption was abnormal. In bone resorption, osteoclasts attach to the bone and dissolve bone mineral in the matrix, a process that appears to proceed normally even in pycnodysostosis. In a second step, known as collagenolysis, peptide bonds in the collagen of the demineralized bone matrix are broken down. The authors expected that this step would be defective in the cells of a patient who lacked cathepsin K, but instead found that it was not, since the patient's osteoclasts showed evidence of bone resorption.

"The results of our study indicate that, against the dogma, cathepsin K is not necessary for osteoclast-mediated bone resorption," the authors state. "The present results and some very recent findings suggest that even total inhibition of cathepsin K does not protect against pathologic bone destruction in arthritis." This indicates that other proteinases may play a role in bone collagen destruction when cathepsin K is not present. The authors conclude: "These findings may be pertinent to our understanding of the functions of cathepsin K inhibitors, which are currently being developed as drugs to treat metabolic bone diseases.


'/>"/>

Contact: Sean Wagner
swagner@wiley.com
781-388-8550
Wiley-Blackwell
Source:Eurekalert

Related medicine news :

1. Penn scientists map molecular regulation of fat-cell genetics
2. Tackling a hard-to-treat childhood cancer by targeting epigenetic changes
3. Tackling Hard-to-treat Childhood Cancer by Targeting Epigenetic Changes
4. Interleukin Genetics to Present at Rodman & Renshaw 10th Annual Healthcare Conference
5. First evidence that prenatal exposure to famine may lead to persistent epigenetic changes
6. If the diabetes has a direct carcinogenetic effect?
7. Genetic Approach Boosts Yeast Infection Treatment
8. Breakthrough Baldness Genetic Test
9. New Genetic Links to Baldness Discovered
10. Genetic Research Offers Insights Into Form of Malaria
11. deCODE Launches deCODE BreastCancer(TM), a Genetic Test to Screen for Risk of the Common Forms of Breast Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... ... 2017 , ... “The Communion of Saints: A Pastor’s Potpourri ... congregations across the United States. “The Communion of Saints” is the creation ... served congregations in seven states throughout his long career of devotion to the ...
(Date:3/23/2017)... ... 23, 2017 , ... A recent report from the National Council on Teacher ... NCTQ report suggests, based on a review of GPA and SAT/ACT requirements at 221 ... the U.S. It argues that this higher bar should be set by states, by ...
(Date:3/23/2017)... , ... March 23, 2017 , ... Texas Physical ... at 960 Gruene Road in Building 2. The clinic is the group’s second in ... PT, says opening the company’s second New Braunfels location brings things full circle for ...
(Date:3/23/2017)... (PRWEB) , ... March 23, 2017 , ... The MBI “Hall of Fame” recognizes the ... acts have had a significant impact on the careers of all others involved. ... Inc. was inducted into the MBI’s Hall of Fame. The induction took place during ...
(Date:3/23/2017)... (PRWEB) , ... March 23, 2017 , ... March is ... that pack a punch when it comes to maintaining good health. Every day, two ... minutes, your kidneys filter every drop of your blood, eliminating waste, regulating fluid levels ...
Breaking Medicine News(10 mins):
(Date:3/23/2017)... March 23, 2017 The key factors ... increasing diabetic population, accelerating economic growth and increasing healthcare expenditure. ... are higher life expectancy of ESRD patients, rising demand for ... However, the expansion of the market is hindered by high ... ...
(Date:3/23/2017)... SANTA BARBARA, Calif. and INDIANAPOLIS ... Company (NYSE: LLY ) and the William ... improve the lives of Latino people affected by diabetes ... "The tremendous burden of diabetes and cardiovascular disease bears ... the United States ," said David Kerr ...
(Date:3/23/2017)... MOINES, Iowa , March 23, 2017   ... and career resource, has partnered with Indiana Biosciences ... Indiana organizations and educational institutions to bring ... with the first-ever BioIndiana Hotbed map, an artistic representation ... framed print was presented to Vice President Mike ...
Breaking Medicine Technology: