Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1016/j.biomaterials.2012.08.028
Title (Primary) The effect of the degree of sulfation of glycosaminoglycans on osteoclast function and signaling pathways
Author Salbach, J.; Kliemt, S.; Rauner, M.; Rachner, T.D.; Goettsch, C.; Kalkhof, S.; von Bergen, M.; Möller, S.; Schnabelrauch, M.; Hintze, V.; Scharnweber, D.; Hofbauer, L.C.
Source Titel Biomaterials
Year 2012
Department PROTEOM
Volume 33
Issue 33
Page From 8418
Page To 8429
Language englisch
Keywords Extracellular matrix (ECM); Chondroitin sulfate; Hyaluronan; Osteoclast; Sulfated glycosaminoglycans; Quantitative proteomics
Abstract To meet the growing need for bone replacement of our aging population, development of new adaptive biomaterials is essential. Collagen and glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are major components of the extracellular matrix (ECM) in bone. We manufactured native and sulfate-modified GAG matrices, evaluated how these components modulate different functions of osteoclasts, the cells that resorb bone, and analyzed the underlying mechanisms. GAGs were tested for their effects on osteoclast adhesion, viability, differentiation, morphology, and resorption as well as proteome alterations using murine RAW264.7 cells and primary human osteoclasts. Native and sulfated GAGs were stable and largely non-cytotoxic. Sulfation of GAGs led to a significant inhibition of osteoclast differentiation and resorption, which was largely dependent on the degree of sulfation of GAGs rather than the monosaccharide composition. Sulfation significantly reduced resorptive function by 14% (CS) and 43% (HA). Highly sulfated GAGs dose-dependently suppressed osteoclast differentiation, osteoclast-specific expression of TRAP, cathepsin K, SWAP-70, and OSCAR by 63–95%, and inhibited proteins involved in cytoskeletal rearrangement. In conclusion, highly sulfated GAGs significantly inhibit various functions of bone-resorbing osteoclasts. Whether these properties locally contribute to improved fracture or bone defect healing needs to be validated in vivo.

Persistent UFZ Identifier
Salbach, J., Kliemt, S., Rauner, M., Rachner, T.D., Goettsch, C., Kalkhof, S., von Bergen, M., Möller, S., Schnabelrauch, M., Hintze, V., Scharnweber, D., Hofbauer, L.C. (2012):
The effect of the degree of sulfation of glycosaminoglycans on osteoclast function and signaling pathways
Biomaterials 33 (33), 8418 - 8429 10.1016/j.biomaterials.2012.08.028