New strategy against osteoporosis
Date:
August 5, 2020
Source:
University of Wu"rzburg
Summary:
An international research team has found a new approach that may be
able to reduce bone loss in osteoporosis and maintain bone health.
FULL STORY ========================================================================== Osteoporosis is the most common age-related bone disease which affects
hundreds of millions of individuals worldwide. It is estimated that one
in three women and one in five men aged over 50 suffer from osteoporotic
bone fractures.
========================================================================== Osteoporosis is caused by excessive activity of bone resorbing cells,
while activity of bone-forming cells is reduced. In healthy individuals,
a balanced activity of these two cell types allows constant bone turnover
to maintain healthy and strong bones.
In osteoporosis, disproportionate bone resorption leads to low bone
mineral density and consequently weak and fracture-prone bones. When
new bone formation is unable to catch up with bone loss, bone eventually weakens, and becomes more prone to fractures.
Current medicines have disadvantages Most current osteoporosis therapies include the use of bisphosphonates, which block the activity of bone
resorbing cells, and thus prevent excessive bone resorption. However,
prolonged treatment with these drugs eliminates the necessary bone
turn-over leading to increased fracture risk and other unwanted side
effects. Therefore, there is an urgent need to develop new strategies
that overcome the limitations of current treatments.
There are now new progresses in this area. They have been developed in
a cooperation of Professors Christoph Winkler (Department of Biological Sciences, National University of Singapore, NUS) and Manfred Schartl (Biocenter, Julius- Maximilians-Universita"t Wu"rzburg, JMU, Germany);
the results have been published in the journal PNAS.
========================================================================== Small protein mobilises bone resorbing cells Using genetic analysis in
a small laboratory fish model, the Japanese medaka (Oryzias latipes),
the research team identified a small protein, the chemokine CXCL9, that,
under osteoporotic conditions, diffuses towards reservoirs that hold
bone resorbing cell precursors. These precursors produce a receptor,
CXCR3, on their cell surface. Upon activation by CXCL9, the precursors
are mobilised and migrate long distances in a highly directed fashion
towards the bone matrix, where they start resorbing bone.
Known inhibitors are highly effective Both CXCL9 and its receptor
CXCR3 have long been known to modulate the migration of immune
cells to inflammation sites, for example in psoriasis and rheumatoid
arthritis. There are several chemical inhibitors blocking CXCR3 activity
that have had little success in clinical tests for the treatment of
psoriasis. The research team showed that these inhibitors are highly
effective in blocking bone resorbing cells' recruitment and protecting
bone from osteoporotic insult.
Finely tuned therapies seem possible The conclusion of the professors
Schartl and Winkler: "Our studies provided new avenues to osteoporosis
therapy. The new strategy allows a fine-tuned modulation of osteoclast
numbers that are recruited to bone matrix rather than a widespread
blockage of osteoclast activity as in traditional therapies. This has
major advantages as excessive bone resorption can be prevented in a
targeted manner but normal bone turn-over will still continue. This
offers potential to avoid increased fracture risks in osteoporosis
patients and to maintain healthy bone for improved quality of life."
Christoph Winkler is an alumnus of JMU. He was a PhD student and
research assistant in Manfred Schartl's team and followed the call for
a professorship in Singapore in 2007. He returned to JMU for a while
in 2016 -- for a sabbatical, financially supported by the Wu"rzburg
University Board. During this time, the ground was prepared for the
cooperation the results of which can now be read in PNAS.
========================================================================== Story Source: Materials provided by University_of_Wu"rzburg. Original
written by Robert Emmerich. Note: Content may be edited for style
and length.
========================================================================== Journal Reference:
1. Quang Tien Phan, Wen Hui Tan, Ranran Liu, Sudha Sundaram, Anita
Buettner,
Susanne Kneitz, Benedict Cheong, Himanshu Vyas, Sinnakaruppan
Mathavan, Manfred Schartl, Christoph Winkler. Cxcl9l and Cxcr3.2
regulate recruitment of osteoclast progenitors to bone matrix in
a medaka osteoporosis model. Proceedings of the National Academy
of Sciences, 2020; 202006093 DOI: 10.1073/pnas.2006093117 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2020/08/200805102032.htm
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