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Store‐operated calcium entry regulate mesenchymal stem cell proliferation
Author(s) -
Maliske Joshua Keith,
Pani Biswaranjan,
Bollimuntha Sunitha,
Ohm Joyce E.,
Singh Brij B.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.571.4
Subject(s) - stim1 , orai1 , microbiology and biotechnology , mesenchymal stem cell , endoplasmic reticulum , trpc1 , chemistry , calcium signaling , voltage dependent calcium channel , stem cell , cellular differentiation , calcium channel , biology , calcium , signal transduction , biochemistry , ion channel , receptor , organic chemistry , gene
Mesenchymal stem cells (MSC) are a unique class of stromal cells which like other stem cells have the special ability to self‐renew and differentiate. MSCs have multi‐lineage differentiation potential, and can be coaxed to differentiate into adipocytes, chondrocytes, osteocytes or neurons in vitro . It is this remarkable plasticity which makes the MSCs important for cell‐based therapy and regenerative applications. Thus, understanding the molecular mechanisms that control growth and differentiation of MSCs is of clinical importance. Calcium (Ca 2+ ) is an essential signaling messenger that modulates a variety of cellular functions ranging from cell growth to differentiation to cell death. One of the prime physiological modalities that regulate cellular Ca 2+ homeostasis is store‐operated calcium entry (SOCE). SOCE represents a universal phenomenon of Ca 2+ influx across the plasma membrane which is triggered, following activation of PM‐GPCRs, by IP3‐mediated depletion of endoplasmic reticulum Ca 2+ stores. Studies from this laboratory and others have suggested the non‐selective cation channel TRPC1 as an integral component of store‐operated Ca 2+ channel (SOC). Further, TRPC1 forms a complex with the recently identified calcium‐selective channel Orai1 and following store‐depletion is activated by the endoplasmic reticulum‐associated Ca 2+ sensor STIM1. The objective of this study was to identify the ‘TRPC1‐STIM1‐Orai1’ component of Ca 2+ signaling and to test the significance of SOCE in MSC proliferation. Using RT‐PCR we identified the expression of TRPC1, STIM1 and Orai1, and co‐immunoprecipitation analysis identified their functional interaction. Further, pharmacological inhibition of SOCE in proliferating MSCs resulted in growth attenuation. In conclusion, our study suggests the ‘TRPC1‐STIM1‐Orai1’ complex as the core SOCE machinery that is critical for MSC proliferation