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