Abstract

The biological activity of osteoblasts and osteoclasts is regulated not only by hormones but also by local growth factors, which are expressed in neighbouring cells or included in bone matrix. Previously, we developed hydroxyapatite (HA) composed of rod-shaped particles using applied hydrothermal methods (HHA), and it revealed mild biodegradability and potent osteoclast homing activity. Here, we compared serum proteins adsorbed to HHA with those adsorbed to conventional HA composed of globular-shaped particles (CHA). The two ceramics adsorbed serum albumin and γ-globulin to similar extents, but affinity for γ-globulin was much greater than that to serum albumin. The chemotactic activity for macrophages of serum proteins adsorbed to HHA was significantly higher than that of serum proteins adsorbed to CHA. Quantitative proteomic analysis of adsorbed serum proteins revealed preferential binding of vitamin D-binding protein (DBP) and complements C3 and C4B with HHA. When implanted with the femur of 8-week-old rats, HHA contained significantly larger amount of DBP than CHA. The biological activity of DBP was analysed and it was found that the chemotactic activity for macrophages was weak. However, DBP-macrophage activating factor, which is generated by the digestion of sugar chains of DBP, stimulated osteoclastogenesis. These results confirm that the microstructure of hydroxyapatite largely affects the affinity for serum proteins, and suggest that DBP preferentially adsorbed to HA composed of rod-shaped particles influences its potent osteoclast homing activity and local bone metabolism.

Highlights

  • Bone metabolism is strictly regulated by the balance of osteogenic activity of osteoblasts and bone resorbing activity of osteoclasts

  • When receptor activator of nuclear factor kappa-B ligand (RANKL) binds to its receptor RANK, which is expressed in osteoclast progenitor cells, osteoclast progenitor cells differentiate into osteoclasts [4]

  • The amount of human serum proteins adsorbed to hydrothermal methods (HHA) was about 20% greater than that adsorbed to composed of globular-shaped particles (CHA) (Fig. 3C)

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Summary

Introduction

Bone metabolism is strictly regulated by the balance of osteogenic activity of osteoblasts and bone resorbing activity of osteoclasts. The biological activities of osteoblasts and osteoclasts are regulated by hormones and by local factors. The importance of hormonal regulation of bone metabolism is obvious considering symp*Correspondence to: Tohru IKEDA, Ph.D., Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. (BMPs), were initially isolated from bone matrix proteins. Osteoblasts in turn express one of the most important osteoclastogenic factors, receptor activator of nuclear factor kappa-B ligand (RANKL). When RANKL binds to its receptor RANK, which is expressed in osteoclast progenitor cells, osteoclast progenitor cells differentiate into osteoclasts [4]. In addition to the coupling of bone formation to resorption described above, many types of a 2013 The Authors

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