PMID- 37152900
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230509
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 10
DP  - 2023
TI  - Hypoxia-induced Wnt/beta-catenin signaling activation in subchondral bone 
      osteoblasts leads to an osteoarthritis-like phenotype of chondrocytes in 
      articular cartilage.
PG  - 1057154
LID - 10.3389/fmolb.2023.1057154 [doi]
LID - 1057154
AB  - Background: Osteoarthritis (OA) is a whole-joint disease and characterized by 
      alterations in the articular cartilage, subchondral bone, ligaments, and synovial 
      membrane. The crosstalk between cartilage and subchondral bone plays a crucial 
      role in the pathogenesis and progression of OA. Hypoxia has been reported to play 
      an important role in cartilage degradation and subchondral bone remodeling in OA. 
      In this study, we aimed to identify the involvement of hypoxia in modifying the 
      osteoblast phenotypes and determine whether these alterations could influence the 
      metabolism of chondrocytes. Methods: First, the levels of Hif-1alpha in subchondral 
      bone of different compartments in patients with OA were assessed using 
      immunohistochemistry (IHC). In in vitro, human primary osteoblasts were cultured 
      under hypoxic and normoxic conditions, and the hypoxic or normoxic conditioned 
      media (HCM and NCM) were used to culture human primary chondrocytes. Then, 
      phenotypic changes in osteoblasts were assessed using reverse 
      transcription-polymerase chain reaction (RT-PCR), Western blotting, and 
      enzyme-linked immunosorbent assay (ELISA). Furthermore, the expression of type II 
      collagen (COL2A1), aggrecan (ACAN), SRY-related high-mobility group-box gene 9 
      (SOX9), matrix metalloproteinase 13 (MMP13), and matrix metalloproteinase 3 
      (MMP3) in chondrocytes was measured using RT-PCR. Finally, the serum levels of 
      Wnt-related proteins were determined using ELISA. Results: Hif-1alpha was 
      significantly increased in severely sclerotic subchondral bone compared to less 
      damaged subchondral bone. beta-Catenin and SOST were identified as upregulated and 
      downregulated in hypoxic osteoblasts, respectively. The hypoxia-induced results 
      were confirmed by ELISA. Stimulating human primary chondrocytes with HCM 
      significantly induced MMP13 and MMP3 and inhibited COL2A1, ACAN, and SOX9 mRNA 
      expression. The serum levels of DKK-1 were significantly increased in human OA. 
      Conclusion: Together, these findings revealed that hypoxia in subchondral bone is 
      a key factor in the crosstalk between chondrocytes and osteoblasts and 
      facilitates the shift of chondrocytes toward an OA-like phenotype probably by 
      activating the Wnt/beta-catenin signaling pathway in osteoblasts.
CI  - Copyright (c) 2023 Li, Tan, Li, Zhang, Liu, Tian and Zhu.
FAU - Li, Fang
AU  - Li F
AD  - Department of Hematology, Peking University Third Hospital, Beijing, China.
FAU - Tan, Qizhao
AU  - Tan Q
AD  - Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
AD  - Department of Orthopaedics, Zibo Central Hospital, Zibo, Shandong, China.
AD  - Engineering Research Center of Bone and Joint Precision Medicine, Ministry of 
      Education, Beijing, China.
FAU - Li, Feng
AU  - Li F
AD  - Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
AD  - Engineering Research Center of Bone and Joint Precision Medicine, Ministry of 
      Education, Beijing, China.
FAU - Zhang, Ke
AU  - Zhang K
AD  - Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
AD  - Engineering Research Center of Bone and Joint Precision Medicine, Ministry of 
      Education, Beijing, China.
AD  - Department of Orthopaedics, Peking University International Hospital, Beijing, 
      China.
FAU - Liu, Zhongjun
AU  - Liu Z
AD  - Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
AD  - Engineering Research Center of Bone and Joint Precision Medicine, Ministry of 
      Education, Beijing, China.
FAU - Tian, Yun
AU  - Tian Y
AD  - Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
AD  - Engineering Research Center of Bone and Joint Precision Medicine, Ministry of 
      Education, Beijing, China.
FAU - Zhu, Tengjiao
AU  - Zhu T
AD  - Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
AD  - Engineering Research Center of Bone and Joint Precision Medicine, Ministry of 
      Education, Beijing, China.
AD  - Department of Orthopaedics, Peking University International Hospital, Beijing, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20230421
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC10160672
OTO - NOTNLM
OT  - Wnt pathway
OT  - articular cartilage
OT  - crosstalk
OT  - hypoxia
OT  - osteoarthritis
OT  - subchondral bone
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/05/08 06:42
MHDA- 2023/05/08 06:43
PMCR- 2023/01/01
CRDT- 2023/05/08 04:09
PHST- 2022/09/29 00:00 [received]
PHST- 2023/03/27 00:00 [accepted]
PHST- 2023/05/08 06:43 [medline]
PHST- 2023/05/08 06:42 [pubmed]
PHST- 2023/05/08 04:09 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 1057154 [pii]
AID - 10.3389/fmolb.2023.1057154 [doi]
PST - epublish
SO  - Front Mol Biosci. 2023 Apr 21;10:1057154. doi: 10.3389/fmolb.2023.1057154. 
      eCollection 2023.