Complex Effect of Hydroxyapatite Nanoparticles on the Differentiation and Functional Activity of Human Pre-Osteoclastic Cells

Abstract

Nanosized hydroxyapatite (HA) is a promising material in clinical applications targeting the bone tissue. NanoHA is able to modulate bone cellular events, which accounts for its potential utility, but also raises safety concerns regarding the maintenance of the bone homeostasis. This work analyses the effects of HA nanoparticles (HAnp) on osteoclastic differentiation and activity, an issue that has been barely addressed. Rod-like HAnp, produced by a hydrothermal precipitation method, were tested on peripheral blood mononuclear cells (PBMC), which contains the CD14+ osteoclastic precursors, in unstimulated or osteoclastogenic-induced conditions. HAnp were added at three time-points during the osteoclastic differentiation pathway, and cell response was evaluated for osteoclastic related parameters. Results showed that HAnp modulated the differentiation and function of osteoclastic cells in a dose-and time-dependent manner. In addition, the effects were dependent on the stage of osteoclastic differentiation. In unstimulated PBMC, HAnp significantly increased osteoclastogenesis, leading to the formation of mature osteoclasts, as evident by the significant increase of TRAP activity, number of TRAP-positive multinucleated cells, osteoclastic gene expression and resorbing ability. However, in a population of mature osteoclasts (formed in osteoclastogenic-induced PBMC cultures), HAnp caused a dose-dependent decrease on the osteoclastic-related parameters. These results highlight the complex effects of HAnp in osteoclastic differentiation and activity, and suggest the possibility of HAnp to modulate/disrupt osteoclastic behavior, with eventual imbalances in the bone metabolism. This should be carefully considered in bone-related and other established and prospective biomedical applications of HAnp.

Calcium Phosphate as a Key Material for Socially Responsible Tissue Engineering

“…Inhibition of proliferation, fusion, and TRAP activity of RAW264.7 cells seeded on biphasic CAP ceramics was also reported [ 134 ] as well as inhibited differentiation of the same cells into multinucleated osteoclasts upon seeding on a collagen scaffold containing HAP [ 135 ]. The complexity of the effects of nanostructured HAP exhibits on osteoclastogenesis is further evident from a study in which HAP did cause a dose-dependent decrease in the osteoclastic gene expression and resorption capacity of mature osteoclasts, but it also had the opposite, augmentative effect on these very same parameters in undifferentiated peripheral blood mononuclear cells [ 136 ]. Moreover, as seen from Figure 8 , this inhibitory effect exhibited by CAP nanoparticles differs depending on the phase composition of CAP and is most pronounced for HAP, the CAP phase naturally present in bone, and is least pronounced for amorphous CAP.…”

Potention of nHAC/PLGA Based Syringetin as Bionano Bone Graft to Improved Osteoinductivity and Osteoconductivitas

“…It can be implemented as a graft material for grafting bone defect secondary to periodontal disease, trauma, tooth extraction, intrabone defects, sinus removal procedures, and so on. 12 Poly lactic-co-glycolic acid (PLGA) is a copolymer compound which is synthesized through the opening of the copolymerization ring of two different monomer compounds that form cyclic dimers (1,4-dioxide-2,5-diones) of lactic acid and glycolic acid. The ratio of the amount between lactic acid and glycocalyric is 50:50.…”

Biological responses to nanomaterials: understanding nano-bio effects on cell behaviors

“…Costa-Rodrigues et al. ( 2014 ) produced rod-like HA nanoparticles by a hydrothermal precipitation method, and analyzed their effects on peripheral blood mononuclear cells (PBMCs) in unstimulated or osteoclastogenic-induced conditions. Results showed that HA nanoparticles modulated the differentiation and function of osteoclastic cells in a dose- and time-dependent manner.…”