Periosteal progenitors contribute to load-induced bone formation in adult mice and require primary cilia to sense mechanical stimulation

Stem Cell Research & Therapy
Emily R MooreChristopher R Jacobs

Abstract

The fully developed adult skeleton adapts to mechanical forces by generating more bone, usually at the periosteal surface. Progenitor cells in the periosteum are believed to differentiate into bone-forming osteoblasts that contribute to load-induced adult bone formation, but in vivo evidence does not yet exist. Furthermore, the mechanism by which periosteal progenitors might sense physical loading and trigger differentiation is unknown. We propose that periosteal osteochondroprogenitors (OCPs) directly sense mechanical load and differentiate into bone-forming osteoblasts via their primary cilia, mechanosensory organelles known to be involved in osteogenic differentiation. We generated a diphtheria toxin ablation mouse model and performed ulnar loading and dynamic histomorphometry to quantify the contribution of periosteal OCPs in adult bone formation in vivo. We also generated a primary cilium knockout model and isolated periosteal cells to study the role of the cilium in periosteal OCP mechanosensing in vitro. Experimental groups were compared using one-way analysis of variance or student's t test, and sample size was determined to achieve a minimum power of 80%. Mice without periosteal OCPs had severely attenuated mechanicall...Continue Reading

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Citations

Aug 4, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Heather M ZannitMatthew J Silva
Jul 29, 2020·Proceedings of the National Academy of Sciences of the United States of America·Dina NavonR Craig Albertson
Aug 6, 2019·Frontiers in Medicine·Roger Pamphlett, Stephen Kum Jew
Dec 10, 2019·Stem Cells International·Emily R MooreChristopher R Jacobs
Sep 16, 2020·Journal of Cellular and Molecular Medicine·Han XiaoHongbin Lu
Feb 10, 2021·NPJ Microgravity·Ken TakahashiKeiji Naruse
Mar 9, 2021·Oral Diseases·Shuang ZhouYao Sun
Sep 14, 2021·Frontiers of Medicine·Sijin LiYao Sun
May 4, 2021·Journal of Orthopaedic Trauma·Benjamin M WheatleyGregory T Altman
Nov 9, 2021·Journal of Dental Research·Z ChinipardazS Yang

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Methods Mentioned

BETA
electrophoresis
PCR
transgenic
dissection

Software Mentioned

Scanco
ImageJ

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