The Fate of Early Perichondrial Cells in Developing Bones

Authors

Yuki Matsushita
Angel Ka Yan Chu
Chiaki Tsutsumi-Arai
Shion Orikasa
Mizuki Nagata
Sunny Y Wong
Joshua D Welch
Wanida Ono
Noriaki Ono

Publication Date

11-28-2022

Journal

Nature Communications

Abstract

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5+ fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5+ fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid hormone-induced bone anabolism. Therefore, early perichondrial cells of the fetal cartilage are destined to become an adipogenic subset of stromal cells in postnatal diaphyseal bone marrow, supporting the theory that the adult bone marrow stromal compartments are developmentally prescribed within the two distinct cells-of-origins of the fetal bone anlage.

Keywords

Adult, Humans, Hedgehog Proteins, Cartilage, Bone and Bones, Bone Development, Chondrocytes

Comments

Supplementary Materials

Data Availability Statement

PMID: 36443296