Dataset Information

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

ABSTRACT: BACKGROUND: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. METHODS: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%. RESULTS:Mice without periosteal OCPs had severely attenuated mechanically induced bone formation and lacked the mineralization necessary for daily skeletal maintenance. Our in vitro results demonstrate that OCPs in the periosteum uniquely sense fluid shear and exhibit changes in osteogenic markers consistent with osteoblast differentiation; however, this response is essentially lost when the primary cilium is absent. CONCLUSIONS:Combined, our data show that periosteal progenitors are a mechanosensitive cell source that significantly contribute to adult skeletal maintenance. More importantly, an OCP population persists in the adult skeleton and these cells, as well as their cilia, are promising targets for bone regeneration strategies.

SUBMITTER: Moore ER

PROVIDER: S-EPMC6042447 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Moore Emily R ER Zhu Ya Xing YX Ryu Han Seul HS Jacobs Christopher R CR

Stem cell research & therapy 20180711 1

<h4>Background</h4>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 osteochondrop ...[more]

PMID: 29996901

Similar Datasets

Project description:Mechanical loading stimulates bone formation. Bone-lining-cell activation and cell proliferation have been implicated in this process. However, the origin of osteoblasts that form bone following mechanical stimulation remains unknown. Our objective was to identity the contributions of activation, differentiation, and proliferation of osteoblast lineage cells to loading-induced periosteal bone formation. Tamoxifen-inducible Osx-Cre-ERT2;Ai9/TdTomato reporter mice (male and female) were aged to young adult (5 months) and middle age (12 months), and were administered tamoxifen for 5 consecutive days to label osterix-lineage cells. Following a 3-week clearance period, mice were subjected to five consecutive bouts of unilateral axial tibial compression. We first confirmed this protocol stimulated an increase in periosteal bone formation that was primarily lamellar apposition. Next, mice received 5-bromo-2'-deoxyuridine (BrdU) in their drinking water daily to label proliferating cells; calcein was given to label active mineralizing surfaces. Tibias were harvested after the fifth loading day and processed for frozen undecalcified histology. The middiaphyseal periosteal surface in the region of peak bone formation was analyzed. Histology revealed both nonloaded and loaded tibias were covered in osterix positive (Osx+) cells on the periosteal surface of both 5- and 12-month-old animals. There was a significant increase in the mineralizing surface (calcein+) covered with Osx+ cells in loaded versus control limbs. Furthermore, nearly all of the mineralizing surfaces (>95%) were lined with Osx+ cells. We also observed approximately 30% of Osx+ cells were also BrdU+, indicating they arose via proliferation. These results show that following mechanical loading, pre-existing cells of the Osx lineage cover the vast majority of surfaces where there is active loading-induced bone formation, and a portion of these cells proliferated in the 5-day loading period. We conclude the initial anabolic response after mechanical loading is based on the activation and proliferation of Osx lineage cells, not the differentiation of progenitor cells. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets