PMID- 37055817
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230415
IS  - 2050-7771 (Print)
IS  - 2050-7771 (Electronic)
IS  - 2050-7771 (Linking)
VI  - 11
IP  - 1
DP  - 2023 Apr 13
TI  - LncRNA AC006064.4-201 serves as a novel molecular marker in alleviating cartilage 
      senescence and protecting against osteoarthritis by destabilizing CDKN1B mRNA via 
      interacting with PTBP1.
PG  - 39
LID - 10.1186/s40364-023-00477-6 [doi]
LID - 39
AB  - BACKGROUND: Osteoarthritis (OA) is the most prevalent age-related disease in the 
      world. Chondrocytes undergo an age-dependent decline in their proliferation and 
      synthetic capacity, which is the main cause of OA development. However, the 
      intrinsic mechanism of chondrocyte senescence is still unclear. This study aimed 
      to investigate the role of a novel long non-coding RNA (lncRNA), AC006064.4-201 
      in the regulation of chondrocyte senescence and OA progression and to elucidate 
      the underlying molecular mechanisms. METHODS: The function of AC006064.4-201 in 
      chondrocytes was assessed using western blotting, quantitative real-time 
      polymerase chain reaction (qRT-PCR), immunofluorescence (IF) and beta-galactosidase 
      staining. The interaction between AC006064.4-201 and polypyrimidine tract-binding 
      protein 1 (PTBP1), as well as cyclin-dependent kinase inhibitor 1B (CDKN1B), was 
      evaluated using RPD-MS, fluorescence in situ hybridization (FISH), RNA 
      immunoprecipitation (RIP) and RNA pull-down assays. Mice models were used to 
      investigate the role of AC006064.4-201 in post-traumatic and age-related OA in 
      vivo. RESULTS: Our research revealed that AC006064.4-201 was downregulated in 
      senescent and degenerated human cartilage, which could alleviate senescence and 
      regulate metabolism in chondrocytes. Mechanically, AC006064.4-201 directly 
      interacts with PTBP1 and blocks the binding between PTBP1 and CDKN1B mRNA, 
      thereby destabilizing CDKN1B mRNA and decreasing the translation of CDKN1B. The 
      in vivo experiments were consistent with the results of the in vitro experiments. 
      CONCLUSIONS: The AC006064.4-201/PTBP1/CDKN1B axis plays an important role in OA 
      development and provides new molecular markers for the early diagnosis and 
      treatment of OA in the future. Schematic diagram of AC006064.4-201 mechanism. A 
      schematic diagram of the mechanism underlying the effect of AC006064.4-201.
CI  - (c) 2023. The Author(s).
FAU - Shen, Panyang
AU  - Shen P
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China.
FAU - Gao, Jun
AU  - Gao J
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China.
FAU - Huang, Shaohan
AU  - Huang S
AD  - Department of Endocrinology, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, 
      China.
FAU - You, Chenan
AU  - You C
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China.
FAU - Wang, Haitao
AU  - Wang H
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China.
FAU - Chen, Pengyu
AU  - Chen P
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China.
FAU - Yao, Teng
AU  - Yao T
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China.
FAU - Gao, Tianyou
AU  - Gao T
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China.
FAU - Zhou, Bohao
AU  - Zhou B
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China.
FAU - Shen, Shuying
AU  - Shen S
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China. 11207057@zju.edu.cn.
AD  - Department of Endocrinology, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, 
      China. 11207057@zju.edu.cn.
FAU - Zhao, Xing
AU  - Zhao X
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China. zhaox@zju.edu.cn.
AD  - Department of Endocrinology, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, 
      China. zhaox@zju.edu.cn.
FAU - Ma, Jianjun
AU  - Ma J
AD  - Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University & Key Laboratory of Musculoskeletal System Degeneration and 
      Regeneration Translational Research of Zhejiang Province, 3 East Qingchun Road, 
      Hangzhou, 310016, Zhejiang Province, China. sealteam@zju.edu.cn.
AD  - Department of Endocrinology, Sir Run Run Shaw Hospital, Medical College of 
      Zhejiang University, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, 
      China. sealteam@zju.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230413
PL  - England
TA  - Biomark Res
JT  - Biomarker research
JID - 101607860
PMC - PMC10099822
OTO - NOTNLM
OT  - CDKN1B
OT  - Osteoarthritis
OT  - PTBP1
OT  - Senescence
OT  - lncRNAs
COIS- The authors declare no competing interests.
EDAT- 2023/04/14 06:00
MHDA- 2023/04/14 06:01
PMCR- 2023/04/13
CRDT- 2023/04/13 23:39
PHST- 2023/01/04 00:00 [received]
PHST- 2023/03/20 00:00 [accepted]
PHST- 2023/04/14 06:01 [medline]
PHST- 2023/04/13 23:39 [entrez]
PHST- 2023/04/14 06:00 [pubmed]
PHST- 2023/04/13 00:00 [pmc-release]
AID - 10.1186/s40364-023-00477-6 [pii]
AID - 477 [pii]
AID - 10.1186/s40364-023-00477-6 [doi]
PST - epublish
SO  - Biomark Res. 2023 Apr 13;11(1):39. doi: 10.1186/s40364-023-00477-6.