Elevated extracellular calcium ions promote proliferation and migration of mesenchymal stem cells via increasing osteopontin expression

Elevated extracellular calcium ions promote proliferation and migration of mesenchymal stem cells via increasing osteopontin expression
Mi Nam Lee, Hee-Su Hwang, Sin-Hye Oh, Amir Roshanzadeh, Jung-Woo Kim, Ju Han Song, Eung-Sam Kim and Jeong-Tae Koh

Abstract

Supplementation of mesenchymal stem cells (MSCs) at sites of bone resorption is required for bone homeostasis
because of the non-proliferation and short lifespan properties of the osteoblasts. Calcium ions (Ca 2+ ) are released from
the bone surfaces during osteoclast-mediated bone resorption. However, how elevated extracellular Ca 2+
concentrations would alter MSCs behavior in the proximal sites of bone resorption is largely unknown. In this study,
we investigated the effect of extracellular Ca 2+ on MSCs phenotype depending on Ca 2+ concentrations. We found
that the elevated extracellular Ca 2+ promoted cell proliferation and matrix mineralization of MSCs. In addition, MSCs
induced the expression and secretion of osteopontin (OPN), which enhanced MSCs migration under the elevated
extracellular Ca 2+ conditions. We developed in vitro osteoclast-mediated bone resorption conditions using mouse
calvaria bone slices and demonstrated Ca 2+ is released from bone resorption surfaces. We also showed that the MSCs
phenotype, including cell proliferation and migration, changed when the cells were treated with a bone resorption-
conditioned medium. These findings suggest that the dynamic changes in Ca 2+ concentrations in the
microenvironments of bone remodeling surfaces modulate MSCs phenotype and thereby contribute to bone
regeneration