PMID- 38081906
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240202
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 6
IP  - 1
DP  - 2023 Dec 11
TI  - Atsttrin regulates osteoblastogenesis and osteoclastogenesis through the TNFR 
      pathway.
PG  - 1251
LID - 10.1038/s42003-023-05635-y [doi]
LID - 1251
AB  - Osteoporosis is a systemic metabolic bone disorder for which inflammatory 
      cytokines play an important role. To develop new osteoporosis treatments, 
      strategies for improving the microenvironment for osteoblast and osteoclast 
      balance are needed. Tumor necrosis factor-alpha (TNF-alpha) plays an important role in 
      the initiation and development of osteoporosis. Atsttrin is an engineered protein 
      derived from the growth factor, progranulin (PGRN). The present study 
      investigates whether Atsttrin affects osteoclast formation and osteoblast 
      formation. Here we show Atsttrin inhibits TNF-alpha-induced osteoclastogenesis and 
      inflammation. Further mechanistic investigation indicates Atsttrin inhibits 
      TNF-alpha-induced osteoclastogenesis through the TNFR1 signaling pathway. Moreover, 
      Atsttrin rescues TNF-alpha-mediated inhibition of osteoblastogenesis via the TNFR1 
      pathway. Importantly, the present study indicates that while Atsttrin cannot 
      directly induce osteoblastogenesis, it can significantly enhance 
      osteoblastogenesis through TNFR2-Akt-Erk1/2 signaling. These results suggest that 
      Atsttrin treatment could potentially be a strategy for maintaining proper bone 
      homeostasis by regulating the osteoclast/osteoblast balance. Additionally, these 
      results provide new insights for other bone metabolism-related diseases.
CI  - (c) 2023. The Author(s).
FAU - Liu, Kaiwen
AU  - Liu K
AUID- ORCID: 0000-0002-4988-4367
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China.
FAU - Wang, Zihao
AU  - Wang Z
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China.
FAU - Liu, Jinbo
AU  - Liu J
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China.
FAU - Zhao, Wei
AU  - Zhao W
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China.
FAU - Qiao, Fei
AU  - Qiao F
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China.
AD  - Department of Pediatric Orthopedic, Dalian Women and Children's Medical 
      Center(group), Dalian, Liaoning, 116012, China.
FAU - He, Qiting
AU  - He Q
AD  - Department of Orthopedics, Honghui Hospital, Xian Jiaotong University, Xian, 
      Shanxi, 710054, China.
FAU - Shi, Jie
AU  - Shi J
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China.
FAU - Meng, Qunbo
AU  - Meng Q
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China.
FAU - Wei, Jianlu
AU  - Wei J
AUID- ORCID: 0000-0003-3166-5227
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China. 18560089157@163.com.
FAU - Cheng, Lei
AU  - Cheng L
AUID- ORCID: 0000-0002-5948-1342
AD  - Department of Orthopedic, Qilu Hospital of Shandong University, Jinan, Shandong, 
      250012, China. chenglei@email.sdu.edu.cn.
LA  - eng
GR  - ZR2019BH071/Natural Science Foundation of Shandong Province (Shandong Provincial 
      Natural Science Foundation)/
GR  - 2019M651064/China Postdoctoral Science Foundation/
GR  - 81900804/National Natural Science Foundation of China (National Science 
      Foundation of China)/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231211
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Progranulins)
SB  - IM
MH  - Humans
MH  - *Osteogenesis
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Progranulins
MH  - *Osteoporosis
PMC - PMC10713527
COIS- The authors declare no competing interests.
EDAT- 2023/12/12 00:42
MHDA- 2023/12/17 09:45
PMCR- 2023/12/11
CRDT- 2023/12/11 23:30
PHST- 2023/02/08 00:00 [received]
PHST- 2023/11/27 00:00 [accepted]
PHST- 2023/12/17 09:45 [medline]
PHST- 2023/12/12 00:42 [pubmed]
PHST- 2023/12/11 23:30 [entrez]
PHST- 2023/12/11 00:00 [pmc-release]
AID - 10.1038/s42003-023-05635-y [pii]
AID - 5635 [pii]
AID - 10.1038/s42003-023-05635-y [doi]
PST - epublish
SO  - Commun Biol. 2023 Dec 11;6(1):1251. doi: 10.1038/s42003-023-05635-y.