Periosteal stem cells control growth plate stem cells during postnatal skeletal growth

Masayuki Tsukasaki, Noriko Komatsu, Takako Negishi-Koga, Nam Cong-Nhat Huynh, Ryunosuke Muro, Yutaro Ando, Yuka Seki, Asuka Terashima, Warunee Pluemsakunthai, Takeshi Nitta, Takashi Nakamura, Tomoki Nakashima, Shinsuke Ohba, Haruhiko Akiyama, Kazuo Okamoto, Roland Baron and Hiroshi Takayanagi ()
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Masayuki Tsukasaki: The University of Tokyo
Noriko Komatsu: The University of Tokyo
Takako Negishi-Koga: Juntendo University Graduate School of Medicine
Nam Cong-Nhat Huynh: The University of Tokyo
Ryunosuke Muro: The University of Tokyo
Yutaro Ando: The University of Tokyo
Yuka Seki: The University of Tokyo
Asuka Terashima: The University of Tokyo
Warunee Pluemsakunthai: The University of Tokyo
Takeshi Nitta: The University of Tokyo
Takashi Nakamura: Tokyo Dental College
Tomoki Nakashima: Tokyo Medical and Dental University
Shinsuke Ohba: Nagasaki University
Haruhiko Akiyama: Gifu University
Kazuo Okamoto: The University of Tokyo
Roland Baron: Harvard School of Dental Medicine
Hiroshi Takayanagi: The University of Tokyo

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract The ontogeny and fate of stem cells have been extensively investigated by lineage-tracing approaches. At distinct anatomical sites, bone tissue harbors multiple types of skeletal stem cells, which may independently supply osteogenic cells in a site-specific manner. Periosteal stem cells (PSCs) and growth plate resting zone stem cells (RZSCs) critically contribute to intramembranous and endochondral bone formation, respectively. However, it remains unclear whether there is functional crosstalk between these two types of skeletal stem cells. Here we show PSCs are not only required for intramembranous bone formation, but also for the growth plate maintenance and prolonged longitudinal bone growth. Mice deficient in PSCs display progressive defects in intramembranous and endochondral bone formation, the latter of which is caused by a deficiency in PSC-derived Indian hedgehog (Ihh). PSC-specific deletion of Ihh impairs the maintenance of the RZSCs, leading to a severe defect in endochondral bone formation in postnatal life. Thus, crosstalk between periosteal and growth plate stem cells is essential for post-developmental skeletal growth.

Date: 2022
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DOI: 10.1038/s41467-022-31592-x

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