Biotechnological approach for systemic delivery of membrane Receptor Activator of NF-κB Ligand (RANKL) active domain into the circulation

Alfredo Cappariello, Riccardo Paone, Antonio Maurizi, Mattia Capulli, Nadia Rucci, Maurizio Muraca, Anna Teti

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Deficiency of Receptor Activator of NF-κB Ligand (RANKL) prevents osteoclast formation causing osteopetrosis. RANKL is a membrane-bound protein cleaved into active soluble (s)RANKL by metalloproteinase 14 (MMP14). We created a bio-device that harbors primary osteoblasts, cultured on 3D hydroxyapatite scaffolds carrying immobilized MMP14 catalytic domain. Scaffolds were sealed in diffusion chambers and implanted in RANKL-deficient mice. Mice received 1 or 2 diffusion chambers, once or twice and were sacrificed after 1 or 2 months from implants. A progressive increase of body weight was observed in the implanted groups. Histological sections of tibias of non-implanted mice were negative for the osteoclast marker Tartrate-Resistant Acid Phosphatase (TRAcP), consistent with the lack of osteoclasts. In contrast, tibias excised from implanted mice showed TRAcP-positive cells in the bone marrow and on the bone surface, these latter morphologically similar to mature osteoclasts. In mice implanted with 4 diffusion chambers total, we noted the highest number and size of TRAcP-positive cells, with quantifiable eroded bone surface and significant reduction of trabecular bone volume. These data demonstrate that our bio-device delivers effective sRANKL, inducing osteoclastogenesis in RANKL-deficient mice, supporting the feasibility of an innovative experimental strategy to treat systemic cytokine deficiencies.

Original languageEnglish
Pages (from-to)58-69
Number of pages12
JournalBiomaterials
Volume46
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Phosphatases
Bone
Acid Phosphatase
Ligands
Osteoclasts
Membranes
Scaffolds
Acids
Cells
Tibia
Osteoblasts
Metalloproteases
Durapatite
Ports and harbors
Hydroxyapatite
Osteopetrosis
Matrix Metalloproteinase 14
Bone and Bones
Equipment and Supplies
Cytokines

Keywords

  • Diffusion chambers
  • Osteoclast
  • Osteopetrosis
  • RANKL
  • Receptor Activator of NF-κB Ligand

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Biotechnological approach for systemic delivery of membrane Receptor Activator of NF-κB Ligand (RANKL) active domain into the circulation. / Cappariello, Alfredo; Paone, Riccardo; Maurizi, Antonio; Capulli, Mattia; Rucci, Nadia; Muraca, Maurizio; Teti, Anna.

In: Biomaterials, Vol. 46, 01.04.2015, p. 58-69.

Research output: Contribution to journalArticle

Cappariello, Alfredo ; Paone, Riccardo ; Maurizi, Antonio ; Capulli, Mattia ; Rucci, Nadia ; Muraca, Maurizio ; Teti, Anna. / Biotechnological approach for systemic delivery of membrane Receptor Activator of NF-κB Ligand (RANKL) active domain into the circulation. In: Biomaterials. 2015 ; Vol. 46. pp. 58-69.
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