Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis model
Calcium phosphate (CaP) is the inorganic part of hard tissues, such as bone, teeth and tendons, and has a high biocompatibility and good biodegradability. Therefore, CaP nanoparticles functionalized with DNA encoding bone anabolic factors are promising carrier-systems for future therapeutic developm...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1101758/full |
| _version_ | 1797900460796936192 |
|---|---|
| author | Nurgul Imangali Viktoriya Sokolova Kathrin Kostka Matthias Epple Christoph Winkler |
| author_facet | Nurgul Imangali Viktoriya Sokolova Kathrin Kostka Matthias Epple Christoph Winkler |
| author_sort | Nurgul Imangali |
| collection | DOAJ |
| description | Calcium phosphate (CaP) is the inorganic part of hard tissues, such as bone, teeth and tendons, and has a high biocompatibility and good biodegradability. Therefore, CaP nanoparticles functionalized with DNA encoding bone anabolic factors are promising carrier-systems for future therapeutic development. Here, we analysed CaP nanoparticles in a genetically modified medaka fish model, where osteoporosis-like lesions can be induced by transgenic expression of receptor activator of nuclear factor kappa-B ligand (Rankl). Rankl-transgenic medaka were used to visualize and understand effects of microinjected functionalized CaP nanoparticles during modulation of osteoclast activity in vivo. For this, we synthetized multi-shell CaP nanoparticles by rapid precipitation of calcium lactate and ammonium hydrogen phosphate followed by the addition of plasmid DNA encoding the osteoclastogenesis inhibitory factor osteoprotegerin-b (Opgb). An additional layer of poly(ethyleneimine) was added to enhance cellular uptake. Integrity of the synthesized nanoparticles was confirmed by dynamic light scattering, scanning electron microscopy and energy dispersive X-ray spectroscopy. Fluorescently labelled CaP nanoparticles were microinjected into the heart, trunk muscle or caudal fins of Rankl-transgenic medaka embryos that expressed fluorescent reporters in various bone cell types. Confocal time-lapse imaging revealed a uniform distribution of CaP nanoparticles in injected tissues and showed that nanoparticles were efficiently taken up by macrophages that subsequently differentiated into bone-resorbing osteoclasts. After Rankl induction, fish injected with Opg-functionalized nanoparticles showed delayed or absent degradation of mineralized matrix, i.e. a lower incidence of osteoporosis-like phenotypes. This is proof of principle that CaP nanoparticles can be used as carriers to efficiently deliver modulatory compounds to osteoclasts and block their activity. |
| first_indexed | 2024-04-10T08:45:19Z |
| format | Article |
| id | doaj.art-edbe6f06f02645769c834206c4382e8b |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T08:45:19Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-edbe6f06f02645769c834206c4382e8b2023-02-22T09:10:17ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-02-011410.3389/fendo.2023.11017581101758Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis modelNurgul Imangali0Viktoriya Sokolova1Kathrin Kostka2Matthias Epple3Christoph Winkler4Department of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, Singapore, SingaporeInorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Essen, GermanyInorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Essen, GermanyInorganic Chemistry and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen, Essen, GermanyDepartment of Biological Sciences and Centre for Bioimaging Sciences, National University of Singapore, Singapore, SingaporeCalcium phosphate (CaP) is the inorganic part of hard tissues, such as bone, teeth and tendons, and has a high biocompatibility and good biodegradability. Therefore, CaP nanoparticles functionalized with DNA encoding bone anabolic factors are promising carrier-systems for future therapeutic development. Here, we analysed CaP nanoparticles in a genetically modified medaka fish model, where osteoporosis-like lesions can be induced by transgenic expression of receptor activator of nuclear factor kappa-B ligand (Rankl). Rankl-transgenic medaka were used to visualize and understand effects of microinjected functionalized CaP nanoparticles during modulation of osteoclast activity in vivo. For this, we synthetized multi-shell CaP nanoparticles by rapid precipitation of calcium lactate and ammonium hydrogen phosphate followed by the addition of plasmid DNA encoding the osteoclastogenesis inhibitory factor osteoprotegerin-b (Opgb). An additional layer of poly(ethyleneimine) was added to enhance cellular uptake. Integrity of the synthesized nanoparticles was confirmed by dynamic light scattering, scanning electron microscopy and energy dispersive X-ray spectroscopy. Fluorescently labelled CaP nanoparticles were microinjected into the heart, trunk muscle or caudal fins of Rankl-transgenic medaka embryos that expressed fluorescent reporters in various bone cell types. Confocal time-lapse imaging revealed a uniform distribution of CaP nanoparticles in injected tissues and showed that nanoparticles were efficiently taken up by macrophages that subsequently differentiated into bone-resorbing osteoclasts. After Rankl induction, fish injected with Opg-functionalized nanoparticles showed delayed or absent degradation of mineralized matrix, i.e. a lower incidence of osteoporosis-like phenotypes. This is proof of principle that CaP nanoparticles can be used as carriers to efficiently deliver modulatory compounds to osteoclasts and block their activity.https://www.frontiersin.org/articles/10.3389/fendo.2023.1101758/fullosteoporosisnanoparticlesbone resorptionRanklosteoprotegerinOPG |
| spellingShingle | Nurgul Imangali Viktoriya Sokolova Kathrin Kostka Matthias Epple Christoph Winkler Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis model Frontiers in Endocrinology osteoporosis nanoparticles bone resorption Rankl osteoprotegerin OPG |
| title | Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis model |
| title_full | Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis model |
| title_fullStr | Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis model |
| title_full_unstemmed | Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis model |
| title_short | Functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka (Oryzias latipes) osteoporosis model |
| title_sort | functionalized calcium phosphate nanoparticles to direct osteoprotegerin to bone lesion sites in a medaka oryzias latipes osteoporosis model |
| topic | osteoporosis nanoparticles bone resorption Rankl osteoprotegerin OPG |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1101758/full |
| work_keys_str_mv | AT nurgulimangali functionalizedcalciumphosphatenanoparticlestodirectosteoprotegerintobonelesionsitesinamedakaoryziaslatipesosteoporosismodel AT viktoriyasokolova functionalizedcalciumphosphatenanoparticlestodirectosteoprotegerintobonelesionsitesinamedakaoryziaslatipesosteoporosismodel AT kathrinkostka functionalizedcalciumphosphatenanoparticlestodirectosteoprotegerintobonelesionsitesinamedakaoryziaslatipesosteoporosismodel AT matthiasepple functionalizedcalciumphosphatenanoparticlestodirectosteoprotegerintobonelesionsitesinamedakaoryziaslatipesosteoporosismodel AT christophwinkler functionalizedcalciumphosphatenanoparticlestodirectosteoprotegerintobonelesionsitesinamedakaoryziaslatipesosteoporosismodel |