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Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells
Author(s) -
Meyers Valerie E.,
Zayzafoon Majd,
Gonda Steve R.,
Gathings William E.,
McDonald Jay M.
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20229
Subject(s) - microbiology and biotechnology , integrin , collagen receptor , focal adhesion , chemistry , protein kinase b , signal transduction , mapk/erk pathway , mesenchymal stem cell , extracellular matrix , biology , receptor , biochemistry
Spaceflight leads to reduced bone mineral density in weight bearing bones that is primarily attributed to a reduction in bone formation. We have previously demonstrated severely reduced osteoblastogenesis of human mesenchymal stem cells (hMSC) following 7 days culture in modeled microgravity (MMG). One potential mechanism for reduced osteoblastic differentiation is disruption of type I collagen (Col I)–integrin interactions and reduced integrin signaling. Integrins are heterodimeric transmembrane receptors that bind extracellular matrix (ECM) proteins and produce signals essential for proper cellular function, survival, and differentiation. Therefore, we investigated the effects of MMG on integrin expression and function in hMSC. We demonstrate that 7 days of culture in MMG leads to reduced expression of the ECM protein, Col I. Conversely, MMG consistently increases Col I‐specific α 2 and β 1 integrin protein expression. Despite this increase in integrin subunit expression, autophosphorylation of adhesion‐dependent kinases, focal adhesion kinase (FAK) and proline‐rich tyrosine kinase 2 (PYK2), is significantly reduced. Activation of Akt protein kinase (Akt) is unaffected by the reduction in FAK activation. However, reduced downstream signaling via the Ras‐mitogen activated protein kinase (MAPK) pathway is evidenced by a reduction in Ras and extracellular signal‐related protein kinase (ERK) activation. Taken together, our findings indicate that MMG decreases integrin/MAPK signaling, which likely contributes to the observed reduction in osteoblastogenesis. © 2004 Wiley‐Liss, Inc.