MSGID: 1:317/3 6440c047   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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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