ECTS2013 Poster Presentations Cell biology: osteoclasts and bone resorption (24 abstracts)
Glycosaminoglycan sulfation is a key regulator of osteoclast biology and osteogenic bone cell signaling
Juliane Salbach-Hirsch 1 , Elena Tsourdi 1 , Nicole Ziegler 1 , Vera Hintze 2 , Dieter Scharnweber 2, , Stephanie Möller 3 , Matthias Schnabelrauch 3, , Martina Rauner 1 & Lorenz Hofbauer 1,
1Division of Endocrinology, Diabetes and Bone Diseases, Dresden University Medical Center, Dresden, Germany; 2Max Bergmann Center of Biomaterials, Technische Universität Dresden, Dresden, Germany; 3Biomaterials Department, INNOVENT e.V., Jena, Germany; 4Jena Center for Soft Matter, Jena, Germany; 5Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
In light of prolonged life expectancy, the need for biomaterials that govern bone regeneration increases. Improved bone regeneration and osseointegration can be achieved by funtionalizing implant materials. The extracellular matrix (ECM) affects differentiation of bone cells and is critical for bone regeneration. Here we assessed the role of the natural occurring bone ECM glycosaminoglycans (GAGs) hyaluronan (HA) and chondroitin sulfate (CS), and their sulfated derivatives, on osteoclast directed effects for implant functionalization.
The impact of native and sulfate-modified GAGs on viability, morphology, differentiation, gene expression and cell signaling was studied using murine primary cells, the murine RAW264.7 and MLO-Y4 cell lines as models for osteoblasts, osteoclasts and osteocytes respectively.
In response to a direct stimulation with 200 μg/ml native and high-sulfated GAGs profound effects on all stages of osteoclast differentiation were observed. GAG sulfate modification increased the viability of osteoclasts (P<0.05). However, tartrate resistant acid phosphatase (TRAP)-staining and immunofluorescence of regular sealing zone structures in osteoclasts were profoundly decreased (P<0.05). This was accompanied by a loss of resorptive activity up to 40% compared to cells exposed to native GAG (P<0.01) and decreased mRNA levels of osteoclastic marker genes, such as cathepsin K, osteoclast-associated receptor, TRAP (P<0.05). The viability of osteoblasts and osteocyte-like cells treated with equal concentrations of GAGs was not affected. These cells showed increased RANKL/OPG ratios (P<0.05) and decreased SOST expression levels (P<0.05). Correspondingly, supernatants collected from these cells suppressed osteoclastogenesis (P<0,05) but did not affect adhesion and viability. Using surface plasmon resonance, we demonstrated that GAGs can directly bind to OPG, but not RANKL, in a sulfation degree dependent manner resulting in modified OPG bioactivity.
In summary, sulfation of GAGs reduces osteoclastogenesis and pro-osteoclastogenic signaling from osteogenic cells and may represent a useful tool to control enhanced osteoclastic activity and bone loss adjacent to implant surfaces.
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Bone Abstracts
ISSN 2052-1219 (online)
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