A transcriptional atlas of the pubertal human growth plate reveals two populations of stem cells and direct effect of growth hormone
gene, generate extensive chondrocyte clones and differentiate into stromal and osteoblastic lineages, confirming their stem cell properties. Human growth plate explant cultures showed that GH directly activates JAK/STAT, TGF-β, and ERK intracellular signaling pathways, inhibits AKT signaling, and stimulates cartilage growth and proliferation of cartilage stem cells and chondrocytes in the proliferative zone. Together, these findings uncover a conserved dual stem cell organization in human and mouse growth plates and define direct mechanisms of GH action, providing a framework for optimizing growth-promoting therapies.
Authors
- Jussi Heinonen
- Claes Ohlsson
- Andrei S. Chagin (ORCID: https://orcid.org/0000-0002-2696-5850)
- Lars Sävendahl (ORCID: https://orcid.org/0000-0003-1067-4976)
- Dana Trompet (ORCID: https://orcid.org/0000-0001-9472-6184)
- Farasat Zaman (ORCID: https://orcid.org/0000-0002-1832-1051)
- Nelson Tsz Long Chu
- Igor I. Adameyko (ORCID: https://orcid.org/0000-0001-5471-0356)
- Ostap A. Dregval (ORCID: https://orcid.org/0000-0002-9939-6492)
- Lei Li (ORCID: https://orcid.org/0000-0002-8026-3665)
- Xin Liu (ORCID: https://orcid.org/0009-0003-4063-7903)
- Baoyi Zhou
- Xin Tian
Institutions
- Karolinska University Hospital (SE)
- Science for Life Laboratory (SE)
- Karolinska Institutet (SE)
- Medical University of Vienna (AT)
- University of Gothenburg (SE)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2026-04-15
- DOI
- https://doi.org/10.1126/scitranslmed.adw3590
- Primary Topic
- Osteoarthritis Treatment and Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Vetenskapsrådet
- Science for Life Laboratory
- Novo Nordisk Fonden
- Uppsala Multidisciplinary Center for Advanced Computational Science