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Map osteoclast activity to different regions of the tibia. be, MIP of a tile scan of the entire exposed tibia. SHG (blue), CSF1R (green), LysM (red). LysM+ and CSF1R+ In Imaris, the cells were divided. Dimensionality reduction was performed on the exported data and used to identify cluster 0 (magenta), cluster 1 (green), cluster 2 (blue), and cluster 3 (white). Clusters were manually mapped to the bone surface using cell segment IDs. barea, volume, sphericity, oblate ellipticity, and xy Location within the identified cluster. Area and volume values are plotted on a logarithmic scale; all other values are plotted on a linear scale. c, pseudocolor density plot of cell volume and sphericity for clusters 0–4. credit: nature protocol (2023). DOI: 10.1038/s41596-023-00894-9
Bones may seem like hard, lifeless structures, but thanks to an innovative imaging technique developed at the Garvan Institute of Medical Research, the cells that live within them can be imaged in more detail than ever before. I did.
This new method allows researchers to study cells inside mouse bones and visualize the entire length of the bone, not just isolated sections. With a new level of visual detail, researchers discovered that osteoclasts, the cells that destroy bone tissue, are more active in some parts of bone than in others. This knowledge could be used to develop new treatments for osteoporosis and dormant cancer cells that can lie dormant in bones for years before being reactivated by osteoclasts.
“Our method provides an unprecedented window into how cells destroy bone and provides a new way to investigate osteoporosis and bone cancer recurrence.” said Professor Tori Huang, Head of the Microscopy Laboratory and Gene Expression Laboratory (IMAGE), Immunologist at St Vincent’s Hospital, Sydney, Co-Director of the Laboratory, Garvan’s Precision Immunology Program, and paperwas announced in nature protocol.
“We are finally able to image processes inside bone that we previously thought were occurring, which were beyond the limits of traditional microscopy techniques. I’m just starting to understand what it means.”
Don’t give disease-causing cells a place to hide
Osteoclasts are essential to the normal bone maintenance and repair process, but when overactive they can lead to excessive destruction known as osteoporosis.
“The interior of living bone is a ‘dark space’ that is difficult to study due to its hard, calcified structure,” said co-lead author Nayan Deger Bhattacharyya, Ph.D., a postdoctoral fellow in the IMAGE Lab. “To understand diseases such as osteoporosis and cancer recurrence, we needed to develop techniques to look inside bone tissue.”
New technology developed at Garvan’s ACRF INCITe Center allows us to image other dynamic cellular processes that were previously hidden within bone.
“Our new imaging method is minimally invasive and allows us to map localized cell populations along the length of the entire bone, rather than just a small section of the mouse model,” said co-authors. said Dr. Wunna Kyaw. I am a student in the IMAGE laboratory.
The researchers tracked different pockets of bone resorption activity in real time as cells “transformed” between actively resorbing osteoclasts and an intermediate cellular state called osteoplasm.
“These bone traits can accumulate during osteoporosis treatment, but as soon as treatment is stopped, activated osteoclasts can rapidly repopulate and promote bone destruction. This may explain the observation in the clinical setting that many osteoporotic patients take the drug denosumab, which inhibits bone resorption by osteoclasts. “When the cells stop taking the drug, they recoil and cause vertebral fractures. We will use imaging to study how this withdrawal effect can be prevented.” Professor Peter Croucher, Head of the Bone Biology Laboratory, said: At Garvan.
The researchers suggest that their method may migrate to bone during cancer treatment and lie dormant there for years, only to be reactivated by osteoclasts that destroy surrounding bone tissue. They say it could also be used to investigate certain cancer cells.
“Being able to see how cells and molecules interact within bone, and one day be able to target them, could provide an important new tool against bone-related diseases,” said Professor Huang. says.
For more information:
Nayan Deger Bhattacharyya et al. Minimally invasive longitudinal in-vivo imaging of cell dynamics in intact long bones; nature protocol (2023). DOI: 10.1038/s41596-023-00894-9