PMID- 34666502
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220427
IS  - 2046-3758 (Print)
IS  - 2046-3758 (Electronic)
IS  - 2046-3758 (Linking)
VI  - 10
IP  - 10
DP  - 2021 Oct
TI  - Ultrasound-targeted simvastatin-loaded microbubble destruction promotes OA 
      cartilage repair by modulating the cholesterol efflux pathway mediated by PPARgamma 
      in rabbits.
PG  - 693-703
LID - 10.1302/2046-3758.1010.BJR-2021-0162.R3 [doi]
AB  - AIMS: To evaluate the effect of ultrasound-targeted simvastatin-loaded 
      microbubble destruction (UTMD (SV) ) for alleviation of the progression of 
      osteoarthritis (OA) in rabbits through modulation of the peroxisome 
      proliferator-activated receptor (PPARgamma). METHODS: In vitro, OA chondrocytes were 
      treated with ultrasound (US), US-targeted microbubble destruction (UTMD), 
      simvastatin (SV), and UTMD (SV) on alternate days for four weeks. Chondrocytes 
      were also treated with PPARgamma inhibitor, PPARgamma inhibitor+ UTMD (SV) , and UTMD 
      (SV) . The cholesterol efflux rate and triglyceride levels were measured using an 
      assay kit and oil red O staining, respectively. In vivo, the OA rabbits were 
      treated with a single intra-articular injection of UTMD, SV, and UTMD (SV) every 
      seven days for four weeks. Cartilage histopathology was assessed by safranin-O 
      staining and the Mankin score. Total cholesterol (TC) and high-density 
      lipoprotein-cholesterol (HDL-C) in rabbit knee synovial fluid were detected by 
      enzyme-marker assay. Aggrecan, collagen II, and PPARgamma expression levels were 
      analyzed by Western blotting (WB). RESULTS: In vitro, UTMD (SV) significantly 
      increased the cholesterol efflux rate and aggrecan, collagen II, and PPARgamma levels 
      in OA chondrocytes; these effects were blocked by the PPARgamma inhibitor. In vivo, 
      UTMD (SV) significantly increased aggrecan, collagen II, PPARgamma, and HDL-C levels, 
      while TC levels and Mankin scores were decreased compared with the UTMD, SV, OA, 
      and control groups. CONCLUSION: UTMD (SV) promotes cartilage extracellular matrix 
      synthesis by modulating the PPARgamma-mediated cholesterol efflux pathway in OA 
      rabbits. Cite this article: Bone Joint Res 2021;10(10):693-703.
FAU - Wang, Xinwei
AU  - Wang X
AUID- ORCID: 0000-0002-4862-0765
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Wang, Danbi
AU  - Wang D
AUID- ORCID: 0000-0003-3264-4962
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Xia, Peng
AU  - Xia P
AUID- ORCID: 0000-0003-3891-3385
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Cheng, Kai
AU  - Cheng K
AUID- ORCID: 0000-0002-3858-0798
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Wang, Qi
AU  - Wang Q
AUID- ORCID: 0000-0002-4904-2442
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Wang, Xiaoju
AU  - Wang X
AUID- ORCID: 0000-0002-1492-8470
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Lin, Qiang
AU  - Lin Q
AUID- ORCID: 0000-0002-4169-4980
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Song, Jiulong
AU  - Song J
AUID- ORCID: 0000-0001-9928-1575
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Chen, Anliang
AU  - Chen A
AUID- ORCID: 0000-0002-2089-6495
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Li, Xueping
AU  - Li X
AUID- ORCID: 0000-0002-1180-3525
AD  - Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical 
      University, Nanjing, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Bone Joint Res
JT  - Bone & joint research
JID - 101586057
EIN - Bone Joint Res. 2022 Apr;11(4):251. PMID: 35475378
PMC - PMC8559971
OTO - NOTNLM
OT  - Cartilage repair
OT  - Cholesterol efflux
OT  - Microbubble
OT  - OA chondrocytes
OT  - Osteoarthritis
OT  - Simvastatin
OT  - Western blot
OT  - aggrecan
OT  - cartilage repair
OT  - chondrocytes
OT  - collagen II
OT  - high-density lipoprotein (HDL)
OT  - rabbits
OT  - staining
EDAT- 2021/10/21 06:00
MHDA- 2021/10/21 06:01
PMCR- 2021/10/20
CRDT- 2021/10/20 05:31
PHST- 2021/10/20 05:31 [entrez]
PHST- 2021/10/21 06:00 [pubmed]
PHST- 2021/10/21 06:01 [medline]
PHST- 2021/10/20 00:00 [pmc-release]
AID - BJR-10-693 [pii]
AID - 10.1302/2046-3758.1010.BJR-2021-0162.R3 [doi]
PST - ppublish
SO  - Bone Joint Res. 2021 Oct;10(10):693-703. doi: 
      10.1302/2046-3758.1010.BJR-2021-0162.R3.