Strontium-Containing Bioactive Glass Nanoparticles Stimulate Osteogenesis and Suppress Osteoclast Formation in Co-Culture.

Abstract

The effect of monodispersed bioactive glass nanoparticles containing strontium (9.4 mol % SrO and 4.4 mol% SrO) and their dissolution products on osteoclast differentiation are investigated in monoculture and in an osteoblast-osteoclast in vitro co-culture system. Under standard conditions, RAW264.7 cells efficiently differentiate into osteoclast-like cells upon RANKL stimulation, making them a well-established monoculture model for osteoclastogenesis. The viability of RAW264.7 cells exposed to nanoparticles is dose- and time-dependent. Indirect co-culture of pre-osteoblast MC3T3-E1 and mouse monocyte RAW264.7 cells is carried out using Millipore cell culture plate inserts, with and without RANKL. Osteoclast differentiation, indicated by tartrate-resistant acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts, is significantly reduced in RAW264.7 cells exposed to Sr-BGNPs and their dissolution products, compared to RANKL-stimulated control cells. Therefore, the observed reduction in osteoclast differentiation following exposure to Sr-BGNPs and their ionic dissolution products indicates a potential inhibitory effect on this process. In co-culture, bioactive glass nanoparticles containing 9.4 mol% SrO₂ promoted differentiation of osteoblasts, relative to basal media and osteogenic media controls, measured as an increase in Alkaline phosphotase (ALP) activity and formation of mineralized matrix, while differentiation of osteoclasts decreased, measured as a reduction in TRAP activity and multinucleated osteoclast formation.