Osteoprogenitor recruitment and differentiation during intracortical bone remodeling of adolescent humans

Pernille van Dijk Christiansen; Christina Møller Andreasen; Bilal Mohamad El-Masri; Kaja Søndergaard Laursen; Jean-Marie Delaisse; Thomas Levin Andersen

doi:10.1016/j.bone.2023.116896

Osteoprogenitor recruitment and differentiation during intracortical bone remodeling of adolescent humans

Bone. 2023 Dec:177:116896. doi: 10.1016/j.bone.2023.116896. Epub 2023 Sep 11.

Authors

Pernille van Dijk Christiansen¹, Christina Møller Andreasen², Bilal Mohamad El-Masri³, Kaja Søndergaard Laursen⁴, Jean-Marie Delaisse⁵, Thomas Levin Andersen⁶

Affiliations

¹ Clinical Cell Biology, Research Unit of Pathology, Department of Pathology, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: pernille.van.dijk@rsyd.dk.
² Clinical Cell Biology, Research Unit of Pathology, Department of Pathology, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Danish Spatial Imaging Consortium (DanSIC). Electronic address: cmandreasen@health.sdu.dk.
³ Clinical Cell Biology, Research Unit of Pathology, Department of Pathology, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Danish Spatial Imaging Consortium (DanSIC). Electronic address: elmasri@health.sdu.dk.
⁴ Department of Forensic Medicine, Aarhus University, Aarhus, Denmark; Danish Spatial Imaging Consortium (DanSIC). Electronic address: kasl@forens.au.dk.
⁵ Clinical Cell Biology, Research Unit of Pathology, Department of Pathology, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark. Electronic address: jean.marie.delaisse@rsyd.dk.
⁶ Clinical Cell Biology, Research Unit of Pathology, Department of Pathology, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Department of Forensic Medicine, Aarhus University, Aarhus, Denmark; Danish Spatial Imaging Consortium (DanSIC). Electronic address: thomas.levin.andersen@rsyd.dk.

PMID: 37699496
DOI: 10.1016/j.bone.2023.116896

Abstract

Background: Recruitment and proliferation of osteoprogenitors during the reversal-resorption phase, and their differentiation into mature bone-forming osteoblasts is crucial for initiation of bone formation during bone remodeling. This study investigates the osteoprogenitors' gradual recruitment, proliferation, and differentiation into bone-forming osteoblasts within intracortical remodeling events of healthy adolescent humans.

Methods: The study was conducted on cortical bone specimens from 11 adolescent human controls - patients undergoing surgery due to coxa valga. The osteoprogenitor recruitment route and differentiation into osteoblasts were backtracked using immunostainings and in situ hybridizations with osteoblastic markers (CD271/NGFR, osterix/SP7, COL3A1 and COL1A1). The osteoblastic cell populations were defined based on the pore surfaces, and their proliferation index (Ki67), density and number/circumference were estimated in multiplex-immunofluorescence (Ki67, TRAcP, CD34) stained sections.

Results: During the reversal-resorption phase, osteoclasts are intermixed with (COL3A1⁺NFGR⁺) osteoblastic reversal cells, which are considered to be osteoprogenitors of (COL1A1⁺SP7⁺) bone-forming osteoblasts. Initiation of bone formation requires a critical density of these osteoprogenitors (43 ± 9 cells/mm), which is reached though proliferation (4.4 ± 0.5 % proliferative) and even more so through recruitment of osteoprogenitors, but challenged by the ongoing expansion of the canal circumference. These osteoprogenitors most likely originate from osteoblastic bone lining cells and mainly lumen osteoprogenitors, which expand their population though proliferation (4.6 ± 0.3 %) and vascular recruitment. These lumen osteoprogenitors resemble canopy cells above trabecular remodeling sites, and like canopy cells they extend above bone-forming osteoblasts where they may rejuvenate the osteoblast population during bone formation.

Conclusion: Initiation of bone formation during intracortical remodeling requires a critical density of osteoprogenitors on eroded surfaces, which is reached though proliferation and recruitment of local osteoprogenitors: bone lining cells and lumen osteoprogenitors.

Keywords: Coupling; Formation; Osteoblasts; Osteoprogenitors; Reversal cells.