To investigate, Yang and his lab traveled to a deer farm in California where they collected samples of early antler…
To investigate, Yang and his lab traveled to a deer farm in California where they collected samples of early antler tissue, which is primarily made up of skeletal stem cells. Antlers grow from the top down; zo als ze groeien, een reservoir of stemcellen blijft bij de top van de antlers, voortdurend te prolifereren. In early development, antler tissue is soft, much like the cartilage of your nose, making cell sampling an easy task for Yang and harmless for the buck.
Terug in de lab, de wetenschappers gebruikten een verscheidenheid van technieken om de genetica achter antlergroei te analyseren, inclusief analyses van RNA, een molecuul dat help om specifieke uit te voeren gene instructions, and other “knock-down” and “over-expression” studies, which inhibit gene function or rev up, respectively. Comparative RNA analyzed between stem cells in human antlers and human stem cells from bone marrow led Yang to a collection of genes that seemed to have a unique expression in antlers. From that pool, he narrowed the search by tampering with gene function, watching to see how different levels of gene expression affected tissue growth in mouse cells.
In mouse cells, Yang saw that when the uhrf1
gene was decommissioned, the bone tissue could still grow, just not as quickly; Only when uhrf1 was fully functional did the scientists see the rapid cell proliferation characteristic of antler growth. Similarly, when s100a10 was overexpressed, calcium deposits increased and the engineered cells more rapidly mineralized.
“Antler regeneration is a unique phenomenon that, for me, is worth studying just out of pure curiosity, but lo and behold, it may have some really interesting applications for human health,” Yang said.
The researchers hope that their insights into antler genes might inform new approaches for treating diseases like osteoporosis. In healthy bones, two types of cells – osteoblasts and osteoclasts – work as opposing forces. Osteoblasts produce new bone tissue, while osteoclasts break down old bone. De två celletyper arbejder i en yin og yang stil til kontinuerlig form og nedbør ben for at bevare balanceret ben struktur. In osteoporosis, osteoclast function overtakes osteoblasts, and the bone starts to break down.
“We are just at the beginning of this research, but our ultimate goal is to figure out how we can apply the same underlying biology that allows for rapid bone regeneration in deer antlers to help treat human bone conditions, such as osteoporosis, “Yang said.
Yang plans to continue researching multiple kinds of those to confirm that uhrf1 and s100a10 back speedy antagonize growth across species. In addition, he plans to test how the genes function in human cell lines, while continuing to parse how ufh1 and s100a10 work on a molecular level, looking into possible functional pathways.
“There is a lot of work to be done, but This could be a unique model of bone regeneration, and our initial work here has begun to lay a foundation for future studies, “Yang said.
Other Stanford co-authors of the paper are postdoctoral scholars Dan Wang, PhD, and Bin Zhang, PhD; Norma Neff, PhD, DNA sequencing core director; Former undergraduate researcher Rashmi Sharma; William Maloney, MD, the Boswell Professor of Orthopedic Surgery and Chair; and professor of bioengineering and applied physics Stephen Quake, PhD.
Peter Yang is a member of Stanford Bio-X, the Stanford Cardiovascular Institute, Stanford ChEM-H, the Stanford Child Health Research Institute and the Stanford Neurosciences Institute .
Scientists from the Tenth People’s Hospital of Tongji University, Calico Life Sciences and the State Key Lab for Molecular Biology of Special Economic Animals also contributed to the study .
The research was funded by the National Institutes of Health (grants R01AR057837, R01AR057837, R01DE021468 and S10RR027431) the Department of Defense, the Boswell Foundation and the AO Foundation.
Stanford’s Department of Orthopedic Surgery also supported the work.