Incorporation of RANKL promotes osteoclast formation and osteoclast activity on β-TCP ceramics.

Choy, John; Albers, Christoph; Siebenrock, Klaus-Arno; Dolder, Silvia; Hofstetter, Wilhelm; Klenke, Frank M. (2014). Incorporation of RANKL promotes osteoclast formation and osteoclast activity on β-TCP ceramics. Bone, 69, pp. 80-88. Elsevier 10.1016/j.bone.2014.09.013

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β-Tricalcium phosphate (β-TCP) ceramics are approved for the repair of osseous defects. In large defects, however, the substitution of the material by authentic bone is inadequate to provide sufficient long-term mechanical stability. We aimed to develop composites of β-TCP ceramics and receptor activator of nuclear factor κ-B ligand (RANKL) to enhance the formation of osteoclasts and promote cell mediated calcium phosphate resorption. RANKL was adsorbed superficially onto β-TCP ceramics or incorporated into a crystalline layer of calcium phosphate by the use of a co-precipitation technique. Murine osteoclast precursors were seeded onto the ceramics. After 15 days, the formation of osteoclasts was quantified cytologically and colorimetrically with tartrate-resistant acidic phosphatase (TRAP) staining and TRAP activity measurements, respectively. Additionally, the expression of transcripts encoding the osteoclast gene products cathepsin K, calcitonin receptor, and of the sodium/hydrogen exchanger NHA2 were quantified by real-time PCR. The activity of newly formed osteoclasts was evaluated by means of a calcium phosphate resorption assay. Superficially adsorbed RANKL did not induce the formation of osteoclasts on β-TCP ceramics. When co-precipitated onto β-TCP ceramics RANKL supported the formation of mature osteoclasts. The development of osteoclast lineage cells was further confirmed by the increased expression of cathepsin K, calcitonin receptor, and NHA2. Incorporated RANKL stimulated the cells to resorb crystalline calcium phosphate. Our in vitro study shows that RANKL incorporated into β-TCP ceramics induces the formation of active, resorbing osteoclasts on the material surface. Once formed, osteoclasts mediate the release of RANKL thereby perpetuating their differentiation and activation. In vivo, the stimulation of osteoclast-mediated resorption may contribute to a coordinated sequence of material resorption and bone formation. Further in vivo studies are needed to confirm the current in vitro findings.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Orthopädische Chirurgie

09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Choy, John; Albers, Christoph; Siebenrock, Klaus-Arno; Dolder, Silvia; Hofstetter, Wilhelm and Klenke, Frank M.

Subjects:

600 Technology > 610 Medicine & health

ISSN:

8756-3282

Publisher:

Elsevier

Language:

English

Submitter:

Verena de Serra Frazao-Bill

Date Deposited:

10 Feb 2015 15:43

Last Modified:

19 Feb 2019 15:13

Publisher DOI:

10.1016/j.bone.2014.09.013

PubMed ID:

25245204

Uncontrolled Keywords:

Beta-TCP ceramics, Bone substitute materials, Osteoclast, RANKL, Resorption

BORIS DOI:

10.7892/boris.62950

URI:

https://boris.unibe.ch/id/eprint/62950

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