PMID- 38508232
OWN - NLM
STAT- MEDLINE
DCOM- 20240405
LR  - 20240405
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 344
DP  - 2024 May 1
TI  - Knockout of formyl peptide receptor 1 reduces osteogenesis and bone healing.
PG  - 122583
LID - S0024-3205(24)00172-3 [pii]
LID - 10.1016/j.lfs.2024.122583 [doi]
AB  - AIMS: Formyl peptide receptor 1 (FPR1), from a G-protein coupled receptor family, 
      was previously well-characterized in immune cells. But the function of FPR1 in 
      osteogenesis and fracture healing was rarely reported. This study, using the FPR1 
      knockout (KO) mouse, is one of the first studies that try to investigate FPR1 
      function to osteogenic differentiation of bone marrow-derived stem cells (BMSCs) 
      in vitro and bone fracture healing in vivo. MATERIALS AND METHODS: Primary BMSCs 
      were isolated from both FPR1 KO and wild type (WT) mice. Cloned mouse BMSCs (D1 
      cells) were used to examine role of FoxO1 in FPR1 regulation of osteogenesis. A 
      closed, transverse fracture at the femoral midshaft was created to compare bone 
      healing between KO and WT mice. Biomechanical and structural properties of femur 
      were compared between healthy WT and KO mice. KEY FINDINGS: FPR1 expression 
      increased significantly during osteogenesis of both primary and cloned BMSCs. 
      Compared to BMSCs from FPR1 KO mice, WT BMSCs displayed considerably higher 
      levels of osteogenic markers as well as mineralization. Osteogenesis by D1 cells 
      was inhibited by either an FPR1 antagonist cFLFLF or a specific inhibitor of 
      FoxO1, AS1842856. In addition, the femur from WT mice had better biomechanical 
      properties than FPR1 KO mice. Furthermore, bone healing in WT mice was remarkably 
      improved compared to FPR1 KO mice analyzed by X-ray and micro-CT. SIGNIFICANCE: 
      These findings indicated that FPR1 played a vital role in osteogenic 
      differentiation and regenerative capacity of fractured bone, probably through the 
      activation of FoxO1 related signaling pathways.
CI  - Copyright (c) 2024. Published by Elsevier Inc.
FAU - Yang, Xinlin
AU  - Yang X
AD  - Dept of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA.
FAU - Xiao, Wan'an
AU  - Xiao W
AD  - Dept of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA; 
      Department of Orthopedics, Shengjing Hospital of China Medical University, 
      Shenyang, Liaoning, China.
FAU - Le, Quang
AU  - Le Q
AD  - Dept of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA.
FAU - Zhang, Zhichang
AU  - Zhang Z
AD  - Dept of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA; 
      Dept of Orthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical 
      University, Wehui 453100, Henan, China.
FAU - Wang, Weicheng
AU  - Wang W
AD  - Dept of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA.
FAU - Lee, Sang-Hyun
AU  - Lee SH
AD  - Dept of Mechanical & Aerospace Engineering, Center for Applied Biomechanics, 
      University of Virginia, Charlottesville, VA, USA.
FAU - Dighe, Abhijit
AU  - Dighe A
AD  - Dept of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA.
FAU - Kerrigan, Jason R
AU  - Kerrigan JR
AD  - Dept of Mechanical & Aerospace Engineering, Center for Applied Biomechanics, 
      University of Virginia, Charlottesville, VA, USA.
FAU - Cui, Quanjun
AU  - Cui Q
AD  - Dept of Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA. 
      Electronic address: qc4q@virginia.edu.
LA  - eng
PT  - Journal Article
DEP - 20240319
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Receptors, Formyl Peptide)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Osteogenesis
MH  - *Receptors, Formyl Peptide/genetics/metabolism
MH  - Mice, Knockout
MH  - Fracture Healing
MH  - Femur/metabolism
MH  - Cell Differentiation
MH  - Bone Marrow Cells
OTO - NOTNLM
OT  - Bone healing
OT  - Bone marrow derived stem cells
OT  - Formyl peptide receptors
OT  - Osteogenesis
COIS- Declaration of competing interest The authors declare that they have no competing 
      interests.
EDAT- 2024/03/21 00:44
MHDA- 2024/04/05 06:44
CRDT- 2024/03/20 20:23
PHST- 2023/09/16 00:00 [received]
PHST- 2024/03/09 00:00 [revised]
PHST- 2024/03/18 00:00 [accepted]
PHST- 2024/04/05 06:44 [medline]
PHST- 2024/03/21 00:44 [pubmed]
PHST- 2024/03/20 20:23 [entrez]
AID - S0024-3205(24)00172-3 [pii]
AID - 10.1016/j.lfs.2024.122583 [doi]
PST - ppublish
SO  - Life Sci. 2024 May 1;344:122583. doi: 10.1016/j.lfs.2024.122583. Epub 2024 Mar 
      19.