| Title |
Cdkn1a deletion or suppression by cyclic stretch enhance the osteogenic potential of bone marrow mesenchymal stem cell-derived cultures |
| Authors |
Juran, Cassandra M ; Žvirblytė, Justina ; Cheng-Campbell, Margareth ; Blaber, Elizabeth A ; Almeida, Eduardo A C |
| DOI |
10.1016/j.scr.2021.102513 |
| Full Text |
|
| Is Part of |
Stem cell research.. Amsterdam : Elsevier. 2021, vol. 56, art. no. 102513, p. [1-12].. ISSN 1873-5061. eISSN 1876-7753 |
| Keywords [eng] |
CDKN1A/P21 ; Cyclic stretch loading ; Mechanotransduction ; Mesenchymal stem cells ; Regeneration ; Single cell transcriptomics |
| Abstract [eng] |
CDKN1A/P21 is a potent inhibitor of cell cycle progression and its overexpression is thought to be associated with inhibition of normal bone regenerative osteogenesis during spaceflight. To test whether CDKN1A/P21 regulates osteogenesis in response to mechanical loading we studied cyclic stretch versus static culture of Cdkn1a-/- (null) or wildtype primary mouse bone marrow osteoprogenitors during 21-day ex-vivo mineralization assays. Cyclically stretched Cdkn1a-/- cells are 3.95-fold more proliferative than wildtype, while static Cdkn1a-/- cells show a 2.50-fold increase. Furthermore, stage-specific single cell RNAseq analyses show expression of Cdkn1a is strongly suppressed by cyclic stretch in early and late osteoblasts, and minimally in the progenitor population. Lastly, both stretch and/or Cdkn1a deletion cause population shift from osteoprogenitors to osteoblasts, also indicating increased differentiation. Collectively, our results support the hypothesis that Cdkn1a constitutively plays a mechano-reversible anti-proliferative role during osteogenesis and suggests a new molecular target to counter regenerative deficits caused by disuse. |
| Published |
Amsterdam : Elsevier |
| Type |
Journal article |
| Language |
English |
| Publication date |
2021 |
| CC license |
|
