Details

Autor(en) / Beteiligte

• La Manna, Federico
• Hanhart, Daniel
• Kloen, Peter
• van Wijnen, Andre J
• Thalmann, George N.
• Kruithof-de Julio, Marianna
• Chouvardas, Panagiotis

Titel

Molecular profiling of osteoprogenitor cells reveals FOS as a master regulator of bone non-union

Ist Teil von

• Gene, 2023-07, Vol.874, p.147481-147481, Article 147481

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• •Cells derived from trabecular bone (HB), healing fracture callus (CA) or fracture nonunion (NU) show homogeneous surface markers expression, but different molecular profiles.•In vitro osteogenic differentiation of cells from NU samples resulted in the highest mineralization compared to those from HB or CA.•Cells from NU samples showed an overactivation of FOS, STAT1, STAT3, JUN and MITF compared to cells from CA.•Increased FOS activity in fracture tissues is associated with the molecular profile of nonunion. Despite the advances in bone fracture treatment, a significant fraction of fracture patients will develop non-union. Most non-unions are treated with surgery since identifying the molecular causes of these defects is exceptionally challenging. In this study, compared with marrow bone, we generated a transcriptional atlas of human osteoprogenitor cells derived from healing callus and non-union fractures. Detailed comparison among the three conditions revealed a substantial similarity of callus and nonunion at the gene expression level. Nevertheless, when assayed functionally, they showed different osteogenic potential. Utilizing longitudinal transcriptional profiling of the osteoprogenitor cells, we identified FOS as a putative master regulator of non-union fractures. We validated FOS activity by profiling a validation cohort of 31 tissue samples. Our work identified new molecular targets for non-union classification and treatment while providing a valuable resource to better understand human bone healing biology.