KDM5C Inhibition Reduces Osteoclast Activity, Increasing Bone Density
Bone tissue is constantly remodeled through the activity of osteoblast cells, depositing extracellular matrix, and osteoclast cells, breaking down extracellular matrix. With age, the balance between these two populations shifts to favor osteoclasts, and the result is loss of bone density leading to osteoporosis. The research community is actively engaged in finding better ways to shift this balance back towards osteoblast activity. Here, researchers describe an approach that inhibits the generation of osteoclast cells.
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, researchers 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 extracellular matrix resorption 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 extracellular matrix resorption process. The result is more bone mass, which ultimately means stronger bones. 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."