Osteoprogenitor recruitment and differentiation during intracortical bone remodeling of adolescent humans

TY - JOUR

T1 - Osteoprogenitor recruitment and differentiation during intracortical bone remodeling of adolescent humans

AU - van Dijk Christiansen, Pernille

AU - Andreasen, Christina Møller

AU - El-Masri, Bilal Mohamad

AU - Laursen, Kaja Søndergaard

AU - Delaisse, Jean Marie

AU - Andersen, Thomas Levin

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

KW - Coupling

KW - Formation

KW - Osteoblasts

KW - Osteoprogenitors

KW - Reversal cells

UR - https://www.scopus.com/pages/publications/85171345192

U2 - 10.1016/j.bone.2023.116896

DO - 10.1016/j.bone.2023.116896

M3 - Journal article

C2 - 37699496

AN - SCOPUS:85171345192

SN - 8756-3282

VL - 177

JO - Bone

JF - Bone

M1 - 116896

ER -