PMID- 33429622
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210112
IS  - 2373-9878 (Electronic)
IS  - 2373-9878 (Linking)
VI  - 3
IP  - 4
DP  - 2017 Apr 10
TI  - Role of Microtubules in Osteogenic Differentiation of Mesenchymal Stem Cells on 
      3D Nanofibrous Scaffolds.
PG  - 551-559
LID - 10.1021/acsbiomaterials.6b00725 [doi]
AB  - Human bone marrow mesenchymal stem cells (MSCs) cultured on three-dimensional 
      (3D) nanofibrous scaffolds are known to undergo osteogenic differentiation even 
      in the absence of soluble osteoinductive factors. Although this process of 
      differentiation has been attributed to the shape that cells assume on the fibrous 
      scaffolds, it is unclear how constriction of cell shape would contribute to the 
      differentiation phenotype. Here, we quantitatively compared cell and nuclear 
      morphologies of cells cultured on 3D poly(epsilon-caprolactone) (PCL) nanofibers (NF) 
      and two-dimensional (2D) flat films using confocal fluorescence microscopy. We 
      discovered that while cells on the 2D films exhibited cellular and nuclear 
      morphologies similar to those cultured on tissue culture polystyrene, cells 
      cultured on the 3D NF showed distinct cell and nuclear morphologies, with lower 
      areas and perimeters, but higher aspect ratios. We next tested the effect of 
      treatment of cells with actin-depolymerizing cytochalasin D and 
      microtubule-depolymerizing nocodazole on these morphologies. In both 2D and 3D 
      scaffolds, actin depolymerization brought about gross changes in cell and nuclear 
      morphologies. Remarkably, microtubule depolymerization resulted in a phenotype 
      similar to actin depolymerization in cells cultured on 3D NF alone, indicating a 
      significant role for the microtubule cytoskeleton in the maintenance of cell 
      shape and structure in 3D. The morphological changes of the nucleus that were 
      apparent upon cytoskeletal perturbation were reflected in the organization of 
      heterochromatin in the nucleus, with MSCs on 3D alone exhibiting a 
      differentiation phenotype. Finally, we tested the effect of cytoskeletal 
      depolymerization on mineralization of cells. Again, we observed higher 
      mineralization in cells cultured on 3D NF, which was lost in cells treated with 
      either cytochalasin D or nocodazole. Taken together, our results suggest that 
      both the actin and microtubule cytoskeletons contribute significantly toward 
      maintenance of cell and nuclear shape in cells cultured on 3D scaffolds, and 
      consequently to their osteogenic differentiation.
FAU - Meka, Sai Rama Krishna
AU  - Meka SRK
AD  - Department of Materials Engineering and  section signCentre for BioSystems Science and 
      Engineering, Indian Institute of Science, Bangalore 560012, India.
FAU - Chacko, Leeba Ann
AU  - Chacko LA
AD  - Department of Materials Engineering and Centre for BioSystems Science and 
      Engineering, Indian Institute of Science, Bangalore 560012, India.
FAU - Ravi, Ashwini
AU  - Ravi A
AD  - Department of Materials Engineering and Centre for BioSystems Science and 
      Engineering, Indian Institute of Science, Bangalore 560012, India.
FAU - Chatterjee, Kaushik
AU  - Chatterjee K
AD  - Department of Materials Engineering and Centre for BioSystems Science and 
      Engineering, Indian Institute of Science, Bangalore 560012, India.
FAU - Ananthanarayanan, Vaishnavi
AU  - Ananthanarayanan V
AUID- ORCID: 0000-0003-2936-7853
AD  - Department of Materials Engineering and Centre for BioSystems Science and 
      Engineering, Indian Institute of Science, Bangalore 560012, India.
LA  - eng
PT  - Journal Article
DEP - 20170224
PL  - United States
TA  - ACS Biomater Sci Eng
JT  - ACS biomaterials science & engineering
JID - 101654670
SB  - IM
OTO - NOTNLM
OT  - cytoskeleton
OT  - nanofibers
OT  - osteogenesis
OT  - stem cells
OT  - tissue scaffolds
EDAT- 2017/04/10 00:00
MHDA- 2017/04/10 00:01
CRDT- 2021/01/12 01:00
PHST- 2021/01/12 01:00 [entrez]
PHST- 2017/04/10 00:00 [pubmed]
PHST- 2017/04/10 00:01 [medline]
AID - 10.1021/acsbiomaterials.6b00725 [doi]
PST - ppublish
SO  - ACS Biomater Sci Eng. 2017 Apr 10;3(4):551-559. doi: 
      10.1021/acsbiomaterials.6b00725. Epub 2017 Feb 24.