The promotion of osteoclastogenesis by sulfated hyaluronan through interference with osteoprotegerin and receptor activator of NF-κB ligand/osteoprotegerin complex formation

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

In order to improve bone regeneration, in particular in aged and multimorbid patients, the development of new adaptive biomaterials and their characterization in terms of their impact on bone biology is warranted. Glycosaminoglycans (GAGs) such as hyaluronan (HA) are major extracellular matrix (ECM) components in bone and may display osteogenic properties that are potentially useful for biomaterial coatings. Using native and synthetically derived sulfate-modified HA, we evaluated how GAG sulfation modulates the activity of two main regulators of osteoclast function: receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). GAGs were tested for their capability to bind to OPG and RANKL using surface plasmon resonance (SPR), ELISA and molecular modeling techniques. Results were validated in an in vitro model of osteoclastogenesis. Sulfated GAGs bound OPG but not RANKL in a sulfate-dependent manner. Furthermore, OPG pre-incubated with different GAGs displayed a sulfate- and dose-dependent loss in bioactivity, possibly due to competition of GAGs for the RANKL/OPG binding site revealing a potential GAG interaction site at the RANKL/OPG interface. In conclusion, high-sulfated GAGs might significantly control osteoclastogenesis via interference with the physiological RANKL/OPG complex formation. Whether these properties can be utilized to improve bone regeneration and fracture healing needs to be validated in vivo.

Details

OriginalspracheEnglisch
Seiten (von - bis)7653-7661
Seitenumfang9
FachzeitschriftBiomaterials
Jahrgang34
Ausgabenummer31
PublikationsstatusVeröffentlicht - Okt. 2013
Peer-Review-StatusJa

Externe IDs

Scopus 84880931573
PubMed 23871544
WOS 000323459100010
ORCID /0000-0002-8691-8423/work/142235977
ORCID /0000-0002-5611-9903/work/142244025
ORCID /0000-0001-7097-9953/work/142255922

Schlagworte

Schlagwörter

  • Animals, Cell Line, Enzyme-Linked Immunosorbent Assay, Hyaluronic Acid/pharmacology, Mice, Osteoclasts/cytology, Osteoprotegerin/metabolism, Receptor Activator of Nuclear Factor-kappa B/metabolism, Surface Plasmon Resonance