Effect of hyaluronan on osteoclast differentiation in mouse bone marrow-derived cells cocultured with primary osteoblasts

Abstract

Glycosaminoglycans (GAG) are major components of the extracellular matrix present in many tissues. In bone, hyaluronan (HA) accounts for 4−7% of total GAG. GAGs have both structural and functional roles in the regulation of biological processes including cellular growth, migration, and differentiation. GAGs also enhance the biological activity of bone morphogenetic proteins (BMPs). HA hydrogel-delivered BMP-2 precomplexed with dermatan sulfate or heparin can induce bone formation in vivo. 8 Furthermore, biglycan regulates osteoclast differentiation through its effect on osteoblasts and their precursors. HA is an unsulfated polymer of repeating D-glucuronic acid and N-acetylglucosamine disaccharide units which regulates cell proliferation, cell motility, and tissue repair. It is a widely used as a diseasemodifying drug for reducing pain associated with osteoarthritis. Evidence for the efficacy of HA in reducing pain has been demonstrated in animal experimental models, in vitro experiments, 21 and clinical trials. Several studies have focused on the possibility that bone regeneration could be induced by the presence of a HA scaffold. 23, 24 For example, HA enhanced BMP-2 induction of osteoblastic differentiation in osteoblast-like cells. 25, 26 The properties of HA differ depending on the molecular mass of the polymer. 27, 28 Huang et al. reported that low molecular mass HA (60 kDa) increased cell growth and osteocalcin mRNA expression, while high molecular mass HA (900 or 2300 kDa) stimulated ALP activity and cell mineralization in rat calvarial osteoblasts. Sasaki et al. applied high molecular mass HA (1900 kDa) to bone wounds following bone marrow ablation and observed maintenance of osteoinductive growth factors within the local environment and accelerated new bone formation via mesenchymal cell differentiation within the wound. However, Ariyoshi et al. reported that low molecular mass HA (<8 kDa) elevated tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell formation, while high molecular mass HA (2500 kDa) down-regulated differentiation of osteoclast-like celEffect of hyaluronan on osteoclast differentiation in mouse bone marrow-derived cells cocultured with primary osteoblasts