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Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes
GSBS Student Publications
  • Henry Huang, University of Massachusetts Medical School
  • Eric S. Veien, University of Massachusetts Medical School
  • Hong Zhang, University of Massachusetts Medical School
  • David C. Ayers, University of Massachusetts Medical School
  • Jie Song, University of Massachusetts Medical School
Student Author(s)
Henry Huang
GSBS Program
Cell Biology
UMMS Affiliation
Department of Orthopedics and Physical Rehabilitation; Department of Cell and Developmental Biology
Date
1-27-2016
Document Type
Article
Abstract

Overexpression of Smad ubiquitin regulatory factor 2 (Smurf2) in chondrocytes was reported to cause spontaneous osteoarthritis (OA) in mice. However, it is unclear whether Smurf2 is involved in bone and cartilage homeostasis and if it is required for OA pathogenesis. Here we characterized age-related changes in the bone and articular cartilage of Smurf2-deficient (MT) mice by microCT and histology, and examined whether reduced Smurf2 expression affected the severity of OA upon surgical destabilization of the medial meniscus (DMM). Using immature articular chondrocytes (iMAC) from MT and wild-type (WT) mice, we also examined how Smurf2 deficiency affects chondrogenic and catabolic gene expressions and Smurf2 and Smurf1 proteins upon TGF-β3 or IL-1β treatment in culture. We found no differences in cortical, subchondral and trabecular bone between WT and MT in young (4 months) and old mice (16-24 months). The articular cartilage and age-related alterations between WT and MT were also similar. However, 2 months following DMM, young MT showed milder OA compared to WT (~70% vs ~30% normal or exhibiting only mild OA cartilage phenotype). The majority of the older WT and MT mice developed moderate/severe OA 2 months after DMM, but a higher subset of aged MT cartilage (27% vs. 9% WT) remained largely normal. Chondrogenic gene expression (Sox9, Col2, Acan) trended higher in MT iMACs than WT with/without TGF-β3 treatment. IL-1β treatment suppressed chondrgenic gene expression, but Sox9 expression in MT remained significantly higher than WT. Smurf2 protein in WT iMACs increased upon TGF-β3 treatment and decreased upon IL-1β treatment in a dose-dependent manner. Smurf1 protein elevated more in MT than WT upon TGF-β3 treatment, suggesting a potential, but very mild compensatory effect. Overall, our data support a role of Smurf2 in regulating OA development but suggest that inhibiting Smurf2 alone may not be sufficient to prevent or consistently mitigate post-traumatic OA across a broad age range.

Rights and Permissions
Citation: Huang H, Veien ES, Zhang H, Ayers DC, Song J. Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes. PLoS One. 2016 Jan 27;11(1):e0148088. doi: 10.1371/journal.pone.0148088. eCollection 2016. PubMed PMID: 26815610; PubMed Central PMCID: PMC4729489. Link to article on publisher's website
Comments

Copyright: © 2016 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Related Resources
Link to article in PubMed
PubMed ID
26815610
Creative Commons License
Creative Commons Attribution 4.0
Citation Information
Henry Huang, Eric S. Veien, Hong Zhang, David C. Ayers, et al.. "Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes" Vol. 11 Iss. 1 (2016) ISSN: 1932-6203
Available at: http://works.bepress.com/jie_song/45/