title: Simultaneous delivery of BMP-2 factor and anti-osteoporotic drugs using hyaluronan-assembled nanocomposite for synergistic regulation on the behaviors of osteoblasts and osteoclasts in vitro.
abstract: To treat the osteoporosis and regulate the biological behaviors of both osteoblasts and osteoclasts, we prepared a natural polysaccharide-derived nanocomposite, containing alendronate-grafted hyaluronate (HA-Aln) and bone morphogenetic protein 2 (BMP-2) and investigated its synergistic regulation on the behaviors of osteoblasts and osteoclasts in vitro. The HA-Aln/BMP-2 nanocomposite was fabricated through the electrostatic interactions between the HA-Aln molecule and BMP-2 molecule. Here, BMP-2 was used to improve the osteoblast-mediated bone formation. Alendronate (Aln), a targeting ligand to bone matrix, was used to inhibit the osteoclast-mediated bone resorption. In vitro results showed that HA-Aln/BMP-2 nanocomposite could effectively maintain the bioactivity of loaded drugs. The osteoblasts that treated with the HA-Aln/BMP-2 nanocomposite presented a higher level of cell motility, alkaline phosphatase (ALP) activity, mineralization capacity, and osteoblast-related gene expressions (runt-related transcription factor 2, osterix, ALP, collagen type I, osteocalcin, and osteopontin), as compared to that of control group. Besides, the RAW264.7 cells that were treated with HA-Aln/BMP-2 nanocomposite showed a lower level of osteoclastic differentiation. Overall, the HA-Aln/BMP-2 nanocomposite exhibits promising potential as an efficient carrier for co-delivery of anti-osteoporotic drug and growth factors to promote osteoblastic differentiation and bone formation while suppressing osteoclastic activity.
authors.affiliation: a Key Laboratory of Biorheological Science and Technology, Ministry of Education , College of Bioengineering, Chongqing University , Chongqing 400044 , P.R. China.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Luo
authors.forename: Xinkun
authors.initials: X
authors.lastname: Shen
authors.forename: Caiyun
authors.initials: C
authors.lastname: Mu
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Cai
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D053761:Nanocomposites / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000517:prevention & control
chemical_list: C525718:BMP2 protein, human; D050071:Bone Density Conservation Agents; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D004338:Drug Combinations; D006820:Hyaluronic Acid
keywords: BMP-2; hyaluronate; osteoblasts; osteoclasts; osteoporosis