PMID- 32066427
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20201214
IS  - 1471-2474 (Electronic)
IS  - 1471-2474 (Linking)
VI  - 21
IP  - 1
DP  - 2020 Feb 17
TI  - Reduced hypertrophy in vitro after chondrogenic differentiation of adult human 
      mesenchymal stem cells following adenoviral SOX9 gene delivery.
PG  - 109
LID - 10.1186/s12891-020-3137-4 [doi]
LID - 109
AB  - BACKGROUND: Mesenchymal stem cell (MSC) based-treatments of cartilage injury are 
      promising but impaired by high levels of hypertrophy after chondrogenic induction 
      with several bone morphogenetic protein superfamily members (BMPs). As an 
      alternative, this study investigates the chondrogenic induction of MSCs via 
      adenoviral gene-delivery of the transcription factor SOX9 alone or in combination 
      with other inducers, and comparatively explores the levels of hypertrophy and end 
      stage differentiation in a pellet culture system in vitro. METHODS: First 
      generation adenoviral vectors encoding SOX9, TGFB1 or IGF1 were used alone or in 
      combination to transduce human bone marrow-derived MSCs at 5 x 10(2) infectious 
      particles/cell. Thereafter cells were placed in aggregates and maintained for 
      three weeks in chondrogenic medium. Transgene expression was determined at the 
      protein level (ELISA/Western blot), and aggregates were analysed histologically, 
      immunohistochemically, biochemically and by RT-PCR for chondrogenesis and 
      hypertrophy. RESULTS: SOX9 cDNA was superior to that encoding TGFB1, the typical 
      gold standard, as an inducer of chondrogenesis in primary MSCs as evidenced by 
      improved lacuna formation, proteoglycan and collagen type II staining, increased 
      levels of GAG synthesis, and expression of mRNAs associated with chondrogenesis. 
      Moreover, SOX9 modified aggregates showed a markedly lower tendency to progress 
      towards hypertrophy, as judged by expression of the hypertrophy markers alkaline 
      phosphatase, and collagen type X at the mRNA and protein levels. CONCLUSION: 
      Adenoviral SOX9 gene transfer induces chondrogenic differentiation of human 
      primary MSCs in pellet culture more effectively than TGFB1 gene transfer with 
      lower levels of chondrocyte hypertrophy after 3 weeks of in vitro culture. Such 
      technology might enable the formation of more stable hyaline cartilage repair 
      tissues in vivo.
FAU - Weissenberger, M
AU  - Weissenberger M
AUID- ORCID: 0000-0003-3551-3204
AD  - Department of Orthopaedic Surgery, Konig-Ludwig-Haus, Center for Musculoskeletal 
      Research, Julius-Maximilians-University, Brettreichstrasse 11, D-97074, Wurzburg, 
      Germany. m-weissenberger.klh@uni-wuerzburg.de.
FAU - Weissenberger, M H
AU  - Weissenberger MH
AD  - Department of Orthopaedic Surgery, Konig-Ludwig-Haus, Center for Musculoskeletal 
      Research, Julius-Maximilians-University, Brettreichstrasse 11, D-97074, Wurzburg, 
      Germany.
AD  - Department of Pathology, Caritas-Hospital, Bad Mergentheim, Germany.
FAU - Gilbert, F
AU  - Gilbert F
AD  - Department of Orthopaedic Surgery, Konig-Ludwig-Haus, Center for Musculoskeletal 
      Research, Julius-Maximilians-University, Brettreichstrasse 11, D-97074, Wurzburg, 
      Germany.
AD  - Department of Orthopaedic Trauma, Hand, Plastic and Reconstructive Surgery, 
      University Hospital Wurzburg, Wurzburg, Germany.
FAU - Groll, J
AU  - Groll J
AD  - Department of Functional Materials in Medicine and Dentistry, 
      Julius-Maximilians-University, Wurzburg, Germany.
FAU - Evans, C H
AU  - Evans CH
AD  - Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN, USA.
FAU - Steinert, A F
AU  - Steinert AF
AD  - Department of Orthopaedic Surgery, Konig-Ludwig-Haus, Center for Musculoskeletal 
      Research, Julius-Maximilians-University, Brettreichstrasse 11, D-97074, Wurzburg, 
      Germany.
AD  - Present address: Department of Orthopaedic, Trauma, Shoulder and Arthroplasty 
      Surgery, Rhon-Klinikum Campus Bad Neustadt, Bad Neustadt a.d. Saale, Germany.
LA  - eng
PT  - Journal Article
DEP - 20200217
PL  - England
TA  - BMC Musculoskelet Disord
JT  - BMC musculoskeletal disorders
JID - 100968565
RN  - 0 (SOX9 Transcription Factor)
RN  - 0 (SOX9 protein, human)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Adult
MH  - Aged
MH  - Cell Differentiation/*physiology
MH  - Cells, Cultured
MH  - Chondrogenesis/*physiology
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Humans
MH  - Hypertrophy
MH  - Male
MH  - Mesenchymal Stem Cells/*physiology
MH  - Middle Aged
MH  - SOX9 Transcription Factor/biosynthesis/*genetics
PMC - PMC7026978
OTO - NOTNLM
OT  - Adenovirus
OT  - Bone marrow
OT  - Cartilage
OT  - Chondrogenesis
OT  - Gene therapy
OT  - Hypertrophy
OT  - Mesenchymal stem cell
OT  - SOX9
COIS- The authors declare that they have no competing interests.
EDAT- 2020/02/19 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/02/17
CRDT- 2020/02/19 06:00
PHST- 2019/11/01 00:00 [received]
PHST- 2020/02/12 00:00 [accepted]
PHST- 2020/02/19 06:00 [entrez]
PHST- 2020/02/19 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/02/17 00:00 [pmc-release]
AID - 10.1186/s12891-020-3137-4 [pii]
AID - 3137 [pii]
AID - 10.1186/s12891-020-3137-4 [doi]
PST - epublish
SO  - BMC Musculoskelet Disord. 2020 Feb 17;21(1):109. doi: 10.1186/s12891-020-3137-4.