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Published on: February 17, 2018
Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for
Kui Chen1, Huan Geng2, Wei Liang2
1Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, P.R. China. xinggm@ihep.ac.cn and University of Chinese Academy of Sciences, Beijing 100049, P.R. China.
Abstract:
Overactivation and excessive differentiation of osteoclasts (OCs) has been implicated in the course of bone metabolism-related diseases. Although fullerenol nanoparticles (fNPs) have been suggested to inhibit OC differentiation and OC function in our previous work, systemic studies on the effect of fNPs on bone diseases, e.g., osteoporosis (OP), in vivo remain elusive. Herein, it is demonstrated that fNPs significantly suppress the differentiation of OCs that derived from the murine bone marrow monocytes and inhibit the formation of the sealing zone by blocking the formation and patterning of podosomes in OCs spatiotemporally. In vivo, fNPs are supposed to be an efficient inhibitor of the overactivation of OCs in a LPS-induced bone erosion mouse model. The therapeutic effect of fNPs on osteoporosis is also investigated in an ovariectomy-induced osteoporosis rat model. The well-organized trabecular bone, the reduction in the number of TRAP positive cells, the improvement of bone-associated parameters, and the mechanical properties all demonstrate that fNPs, similar to diphosphonates, can be a promising candidate for the effective treatment of osteoporosis.
Insights
Fullerenol nanoparticles (fNPs) effectively inhibit osteoclast differentiation and function. In vivo studies show fNPs treat osteoporosis by improving bone structure and mechanical properties, offering a promising therapeutic candidate.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Bone Biology
Background:
- Osteoclast (OC) overactivation contributes to bone metabolism diseases like osteoporosis (OP).
- Previous work suggested fullerenol nanoparticles (fNPs) inhibit OC differentiation and function.
- Systemic in vivo studies on fNPs for bone diseases, particularly OP, were lacking.
Purpose of the Study:
- To investigate the in vivo therapeutic effects of fNPs on osteoporosis.
- To evaluate fNPs' ability to suppress osteoclast differentiation and function in disease models.
- To assess fNPs' potential as a treatment for osteoporosis.
Main Methods:
- Investigated fNP effects on murine bone marrow monocyte-derived OCs in vitro.
- Assessed fNPs in a lipopolysaccharide (LPS)-induced bone erosion mouse model.
- Evaluated fNPs in an ovariectomy-induced osteoporosis rat model.
Main Results:
- fNPs significantly suppressed OC differentiation and podosome formation in vitro.
- fNPs inhibited OC overactivation in the LPS-induced bone erosion model.
- In the osteoporosis model, fNPs improved trabecular bone organization, reduced TRAP-positive cells, enhanced bone parameters, and improved mechanical properties.
Conclusions:
- fNPs effectively inhibit osteoclast differentiation and function, both in vitro and in vivo.
- fNPs demonstrate significant therapeutic potential for treating osteoporosis.
- fNPs show promise as an effective osteoporosis treatment, comparable to diphosphonates.
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