Osteoporosis treatments may benefit from discovery of key driver of low
bone density

Date:
April 19, 2023
Source:
Van Andel Research Institute
Summary:
Scientists have pinpointed a key driver of low bone density, a
discovery that may lead to improved treatments with fewer side
effects for women with osteoporosis. The findings reveal that
loss of an epigenetic modulator, KDM5C, preserves bone mass in
mice. KDM5C works by altering epigenetic 'marks,' which are akin
to 'on' and 'off' switches that ensure the instructions written
in DNA are used at the right time and in the right place.


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FULL STORY ==========================================================================
Van Andel Institute scientists have pinpointed a key driver of low bone density, a discovery that may lead to improved treatments with fewer
side effects for women with osteoporosis.


==========================================================================
The findings are described in a study published this month in Science
Advances by VAI Associate Professors Connie M. Krawczyk, Ph.D., and Tao
Yang, Ph.D.

Their research reveals that loss of an epigenetic modulator, KDM5C,
preserves bone mass in mice. KDM5C works by altering epigenetic "marks,"
which are akin to "on" and "off" switches that ensure the instructions
written in DNA are used at the right time and in the right place.

"Osteoporosis is a common disease that can have debilitating
outcomes," Yang said. "KDM5C is a promising target to treat low
bone mass in women because it is highly specific. We're hopeful that
our findings will contribute to improved therapies." Nearly 19% of
U.S. women aged 50 and older have osteoporosis in their hips and lower
spines. Osteoporosis-associated weakening of the bones increases the risk
of fractures and poses significant risks to health and quality of life.

Several medications are approved to treat osteoporosis but fears of rare, severe side effects often are a barrier for their use. Treatments that
leverage the hormone estrogen also are available, but are only recommended
for low-dose, short-term use due in part to associations with cancer risk.

It is well-established that women experience disproportionately lower bone
mass than men throughout their lives. Loss of bone mass accelerates with menopause, increasing the risk of osteoporosis and associated fractures
for women as they age.

To figure out why this happens, Krawczyk, Yang and their teams looked at
the differences in the ways bone is regulated in male and female mice,
which share many similarities with humans and are important models for
studying health and disease. They focused on specialized cells called osteoclasts, which help maintain bone health by breaking down and
recycling old bone.

The researchers found reducing KDM5C disrupted cellular energy production
in osteoclasts, which slowed down the recycling process and preserved
bone mass.

Importantly, KDM5C is linked to X chromosomes, which means it is more
active in females than in males.

"Lowering KDM5C levels is like flipping a switch to stop an overactive recycling process. The result is more bone mass, which ultimately means stronger bones," Krawczyk said. "We're very excited about this work and
look forward to carrying out future studies to refine our findings. At
the end of the day, we hope these insights make a difference for
people with osteoporosis." This study was supported in part by VAI's
Employee Impact Campaign, a philanthropic giving program sustained by VAI employees. This critical funding supports innovative and collaborative
projects at the Institute.

* RELATED_TOPICS
o Health_&_Medicine
# Osteoporosis # Women's_Health # Bone_and_Spine #
Menopause # Leukemia # Medical_Topics # Chronic_Illness
# Diseases_and_Conditions
* RELATED_TERMS
o Osteoporosis o Bone_marrow o Lead o Bone_fracture
o Deep_brain_stimulation o Introduction_to_genetics o
Bone_marrow_transplant o Adult_stem_cell

========================================================================== Story Source: Materials provided by Van_Andel_Research_Institute. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Huadie Liu, Lukai Zhai, Ye Liu, Di Lu, Alexandra Vander Ark,
Tao Yang,
Connie M. Krawczyk. The histone demethylase KDM5C controls female
bone mass by promoting energy metabolism in osteoclasts. Science
Advances, 2023; 9 (14) DOI: 10.1126/sciadv.adg0731 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/04/230419125102.htm

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