<p>This study investigated the regulatory effects of strontium-substituted hydroxyapatite (SrHAp) on bone cell regulation, with a specific focus on osteoblast and osteoclast activities. X-ray diffraction verified the successful incorporation of strontium into the hydroxyapatite lattice, confirming the high phase stability despite the presence of a minor amount of CaO. SrHAp nanoparticles with a Sr/Ca molar ratio of 0.417 and a (Ca+Sr)/P ratio of 1.73 were synthesized. The resulting material exhibited a zeta potential of -14.9 mV and an average particle size of 712.6 nm. Cell viability assays revealed that SrHAp concentrations of 100 μg/mL for HOS cells and up to 1000 μg/mL for RAW 264.7 cells were not cytotoxic. Furthermore, SrHAp treatment significantly reduced basal reactive oxygen species levels in HOS cells, suggesting its antioxidant capacity. Our results demonstrated that SrHAp significantly promoted osteoblast differentiation and mineralization, as evidenced by increased calcium deposition detected using Alizarin Red S staining and the upregulation of osteogenic markers, including RUNX2 and osteocalcin. Moreover, SrHAp effectively inhibited RANKL-induced osteoclastogenesis. The morphological analysis of RANKL-treated RAW 264.7 cells revealed a reduction in TRAP-positive multinucleated cells, and this result was supported by decreased TRAP activity. Mechanistic investigations revealed that SrHAp interfered with the RANKL/TRAF6/NF-κB signaling pathway, leading to the downregulation of the master transcription factor NFATc1. In conclusion, SrHAp nanoparticles exhibit dual functions, as they promote osteoblastic mineralization while concurrently arresting osteoclast differentiation. This balanced regulation highlights the potential of SrHAp as a bioactive ceramic for the treatment of osteoporosis and for advanced bone regeneration.</p><p></p>

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Strontium-substituted hydroxyapatite nanoparticles as dual-function regulators of osteoblast mineralization and RANKL-induced osteoclastogenesis

  • Shiao-Wen Tsai,
  • Cheng Li,
  • Shu-ting Lee,
  • Pai-An Hwang,
  • Fu-Yin Hsu

摘要

This study investigated the regulatory effects of strontium-substituted hydroxyapatite (SrHAp) on bone cell regulation, with a specific focus on osteoblast and osteoclast activities. X-ray diffraction verified the successful incorporation of strontium into the hydroxyapatite lattice, confirming the high phase stability despite the presence of a minor amount of CaO. SrHAp nanoparticles with a Sr/Ca molar ratio of 0.417 and a (Ca+Sr)/P ratio of 1.73 were synthesized. The resulting material exhibited a zeta potential of -14.9 mV and an average particle size of 712.6 nm. Cell viability assays revealed that SrHAp concentrations of 100 μg/mL for HOS cells and up to 1000 μg/mL for RAW 264.7 cells were not cytotoxic. Furthermore, SrHAp treatment significantly reduced basal reactive oxygen species levels in HOS cells, suggesting its antioxidant capacity. Our results demonstrated that SrHAp significantly promoted osteoblast differentiation and mineralization, as evidenced by increased calcium deposition detected using Alizarin Red S staining and the upregulation of osteogenic markers, including RUNX2 and osteocalcin. Moreover, SrHAp effectively inhibited RANKL-induced osteoclastogenesis. The morphological analysis of RANKL-treated RAW 264.7 cells revealed a reduction in TRAP-positive multinucleated cells, and this result was supported by decreased TRAP activity. Mechanistic investigations revealed that SrHAp interfered with the RANKL/TRAF6/NF-κB signaling pathway, leading to the downregulation of the master transcription factor NFATc1. In conclusion, SrHAp nanoparticles exhibit dual functions, as they promote osteoblastic mineralization while concurrently arresting osteoclast differentiation. This balanced regulation highlights the potential of SrHAp as a bioactive ceramic for the treatment of osteoporosis and for advanced bone regeneration.