PMID- 31967113
OWN - NLM
STAT- MEDLINE
DCOM- 20201027
LR  - 20201027
IS  - 2047-4849 (Electronic)
IS  - 2047-4830 (Linking)
VI  - 8
IP  - 6
DP  - 2020 Mar 17
TI  - Identification of a prolonged action molecular GLP-1R agonist for the treatment 
      of femoral defects.
PG  - 1604-1614
LID - 10.1039/c9bm01426h [doi]
AB  - Autografts are still regarded as the gold standard treatment for bone defects but 
      they require additional surgery that causes pain for the patient. Thus, 
      alternatives that can substitute for grafts are required. In the present study, a 
      novel poly-GLP-1 molecule was developed using a polymeric pro-drug strategy which 
      was found to accelerate bone healing in a mouse femoral defect model. 
      Furthermore, the poly-GLP-1 molecule induced osteogenesis and inhibited 
      adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). The results 
      demonstrate that poly-GLP-1 promoted M2 polarization of bone marrow-derived 
      macrophages (BMDMs) and increased the levels of TGF-beta1 in the bone marrow, 
      resulting in the migration of an increased number of CD29 + Sca-1 + BMSCs to the 
      bone surface. Finally, we found that poly-GLP-1 facilitated the migration of 
      BMSCs due to transduction of the Smad2 signaling pathway, causing increased 
      numbers of CD31 + Endomucin + endothelial cells in bone marrow that promoted bone 
      formation. These results support poly-GLP-1 as a potential bone-healing agent and 
      suggest that it may play a promising role in the clinical treatment of fracture 
      repair.
FAU - Wang, Ning
AU  - Wang N
AUID- ORCID: 0000-0002-6607-602X
AD  - Department of Pharmacology, School of Pharmacy, Fourth Military Medical 
      University, Xi'an, Shaanxi, China. maxuel@fmmu.edu.cn mjrfmmu@fmmu.edu.cn and 
      Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, China. guozheng@fmmu.edu.cn lxkfmmu@163.com.
FAU - Liu, Xuanchen
AU  - Liu X
AD  - College of Animal Science and Technology, Northwest A&F University, Yangling, 
      Shaanxi, China and Department of Nutrition, Tangdu Hospital, Fourth Military 
      Medical University, Xi'an, Shaanxi, China.
FAU - Shi, Lei
AU  - Shi L
AD  - Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, China. guozheng@fmmu.edu.cn lxkfmmu@163.com.
FAU - Liu, Yanwu
AU  - Liu Y
AD  - Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, China. guozheng@fmmu.edu.cn lxkfmmu@163.com.
FAU - Guo, Shuo
AU  - Guo S
AD  - Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, China. guozheng@fmmu.edu.cn lxkfmmu@163.com.
FAU - Liu, Wenwen
AU  - Liu W
AD  - Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, China. guozheng@fmmu.edu.cn lxkfmmu@163.com.
FAU - Li, Xiaokang
AU  - Li X
AD  - Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, China. guozheng@fmmu.edu.cn lxkfmmu@163.com.
FAU - Meng, Jingru
AU  - Meng J
AD  - Department of Pharmacology, School of Pharmacy, Fourth Military Medical 
      University, Xi'an, Shaanxi, China. maxuel@fmmu.edu.cn mjrfmmu@fmmu.edu.cn.
FAU - Ma, Xue
AU  - Ma X
AD  - Department of Pharmacology, School of Pharmacy, Fourth Military Medical 
      University, Xi'an, Shaanxi, China. maxuel@fmmu.edu.cn mjrfmmu@fmmu.edu.cn.
FAU - Guo, Zheng
AU  - Guo Z
AD  - Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 
      Xi'an, Shaanxi, China. guozheng@fmmu.edu.cn lxkfmmu@163.com.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biomater Sci
JT  - Biomaterials science
JID - 101593571
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Polymers)
SB  - IM
MH  - Adipogenesis/drug effects
MH  - Animals
MH  - Cell Polarity/drug effects
MH  - Femur/drug effects/*injuries/metabolism
MH  - Glucagon-Like Peptide-1 Receptor/*agonists
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cells/*cytology/drug effects
MH  - Mice
MH  - *Osteogenesis
MH  - Polymers/*administration & dosage/chemistry/pharmacology
MH  - Random Allocation
MH  - Signal Transduction/drug effects
MH  - Treatment Outcome
MH  - Wound Healing/drug effects
EDAT- 2020/01/23 06:00
MHDA- 2020/10/28 06:00
CRDT- 2020/01/23 06:00
PHST- 2020/01/23 06:00 [pubmed]
PHST- 2020/10/28 06:00 [medline]
PHST- 2020/01/23 06:00 [entrez]
AID - 10.1039/c9bm01426h [doi]
PST - ppublish
SO  - Biomater Sci. 2020 Mar 17;8(6):1604-1614. doi: 10.1039/c9bm01426h.