The fate of early perichondrial cells in developing bones

Yuki Matsushita, Angel Ka Yan Chu, Chiaki Tsutsumi-Arai, Shion Orikasa, Mizuki Nagata, Sunny Y. Wong, Joshua D. Welch, Wanida Ono and Noriaki Ono ()
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Yuki Matsushita: University of Texas Health Science Center at Houston School of Dentistry
Angel Ka Yan Chu: University of Michigan
Chiaki Tsutsumi-Arai: University of Texas Health Science Center at Houston School of Dentistry
Shion Orikasa: University of Texas Health Science Center at Houston School of Dentistry
Mizuki Nagata: University of Texas Health Science Center at Houston School of Dentistry
Sunny Y. Wong: University of Michigan Medical School
Joshua D. Welch: University of Michigan
Wanida Ono: University of Texas Health Science Center at Houston School of Dentistry
Noriaki Ono: University of Texas Health Science Center at Houston School of Dentistry

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34804-6

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