PMID- 33543485
OWN - NLM
STAT- MEDLINE
DCOM- 20210524
LR  - 20210524
IS  - 1749-6632 (Electronic)
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1490
IP  - 1
DP  - 2021 Apr
TI  - Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 
      diabetes mellitus.
PG  - 77-89
LID - 10.1111/nyas.14568 [doi]
AB  - Type 2 diabetes mellitus (T2DM) significantly increases bone fragility and 
      fracture risk. Progranulin (PGRN) promotes bone fracture healing in both 
      physiological and type 1 diabetic conditions. The present study aimed to 
      investigate the role of PGRN in T2DM bone fracture healing. MKR mice (with an 
      FVB/N genetic background) were used as the T2DM model. Drill-hole and Bonnarens 
      and Einhorn models were used to investigate the role of PGRN in T2DM fracture 
      healing in vivo. Primary bone marrow cells were isolated for molecular and 
      signaling studies, and reverse transcription-polymerase chain reaction, 
      immunohistochemical staining, and western blotting were performed to assess PGRN 
      effects in vitro. PGRN mRNA and protein expression were upregulated in the T2DM 
      model. Local administration of recombinant PGRN effectively promoted T2DM bone 
      fracture healing in vivo. Additionally, PGRN could induce anabolic metabolism 
      during endochondral ossification through the TNFR2-Akt and Erk1/2 pathways. 
      Furthermore, PGRN showed anti-inflammatory activity in the T2DM bone regeneration 
      process. These findings suggest that local administration of exogenous PGRN may 
      be an alternative strategy to support bone regeneration in patients with T2DM. 
      Additionally, PGRN might hold therapeutic potential for other TNFR-related 
      metabolic disorders.
CI  - (c) 2021 New York Academy of Sciences.
FAU - Ding, Yuanjing
AU  - Ding Y
AD  - Department of Orthopaedic Surgery, New York University Medical Center, New York, 
      New York.
AD  - Department of Orthopaedic Surgery, Jinan Central Hospital, Cheeloo College of 
      Medicine, Shandong University, Jinan, Shandong, China.
FAU - Wei, Jianlu
AU  - Wei J
AD  - Department of Orthopaedic Surgery, New York University Medical Center, New York, 
      New York.
AD  - Department of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, Shandong, China.
FAU - Hettinghouse, Aubryanna
AU  - Hettinghouse A
AD  - Department of Orthopaedic Surgery, New York University Medical Center, New York, 
      New York.
FAU - Li, Guangfei
AU  - Li G
AD  - Department of Orthopaedic Surgery, New York University Medical Center, New York, 
      New York.
FAU - Li, Xin
AU  - Li X
AD  - College of Dentistry, New York University, New York, New York.
FAU - Einhorn, Thomas A
AU  - Einhorn TA
AD  - Department of Orthopaedic Surgery, New York University Medical Center, New York, 
      New York.
FAU - Liu, Chuan-Ju
AU  - Liu CJ
AUID- ORCID: 0000-0002-7181-8032
AD  - Department of Orthopaedic Surgery, New York University Medical Center, New York, 
      New York.
AD  - Department of Cell Biology, New York University School of Medicine, New York, New 
      York.
LA  - eng
GR  - R01 AR062207/AR/NIAMS NIH HHS/United States
GR  - R01 NS103931/NS/NINDS NIH HHS/United States
GR  - 1R01NS10393/National Institute of Health/
GR  - R01 AR061484/AR/NIAMS NIH HHS/United States
GR  - R01 AR076900/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210204
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Anabolic Agents)
RN  - 0 (Progranulins)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tnf protein, mouse)
RN  - 0 (Tnfrsf1b protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Anabolic Agents/therapeutic use
MH  - Animals
MH  - Bone Regeneration/*drug effects
MH  - Diabetes Mellitus, Type 2/*pathology
MH  - Fracture Healing/*drug effects
MH  - Fractures, Bone/*drug therapy
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Osteogenesis/*drug effects
MH  - Progranulins/*therapeutic use
MH  - Receptors, Tumor Necrosis Factor, Type II/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC8138780
MID - NIHMS1699489
OTO - NOTNLM
OT  - TNF-alpha
OT  - impaired fracture healing
OT  - progranulin
OT  - tumor necrosis factor receptors
OT  - type 2 diabetes
COIS- Conflicts of interest The authors have no conflicts of interest to declare.
EDAT- 2021/02/06 06:00
MHDA- 2021/05/25 06:00
PMCR- 2021/05/21
CRDT- 2021/02/05 06:06
PHST- 2021/01/08 00:00 [revised]
PHST- 2020/09/02 00:00 [received]
PHST- 2021/01/15 00:00 [accepted]
PHST- 2021/02/06 06:00 [pubmed]
PHST- 2021/05/25 06:00 [medline]
PHST- 2021/02/05 06:06 [entrez]
PHST- 2021/05/21 00:00 [pmc-release]
AID - 10.1111/nyas.14568 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2021 Apr;1490(1):77-89. doi: 10.1111/nyas.14568. Epub 2021 Feb 
      4.