Dataset Information

Combinatorial Surface Roughness Effects on Osteoclastogenesis and Osteogenesis.

ABSTRACT: Implant surface properties are a key factor in bone responses to metallic bone implants. In view of the emerging evidence on the important role of osteoclasts in bone regeneration, we here studied how surface roughness affects osteoclastic differentiation and to what extent these osteoclasts have stimulatory effects on osteogenic differentiation of osteoprogenitor cells. For this, we induced osteoclasts derived from RAW264.7 cell line and primary mouse macrophages on titanium surfaces with different roughness ( R_a 0.02-3.63 ?m) and analyzed osteoclast behavior in terms of cell number, morphology, differentiation, and further anabolic effect on osteoblastic cells. Surfaces with different roughness induced the formation of osteoclasts with distinct phenotypes, based on total osteoclast numbers, morphology, size, cytoskeletal organization, nuclearity, and osteoclastic features. Furthermore, these different osteoclast phenotypes displayed differential anabolic effects toward the osteogenic differentiation of osteoblastic cells, for which the clastokine CTHRC1 was identified as a causative factor. Morphologically, osteoclast potency to stimulate osteogenic differentiation of osteoblastic cells was found to logarithmically correlate with the nuclei number per osteoclast. Our results demonstrate the existence of a combinatorial effect of surface roughness, osteoclastogenesis, and osteogenic differentiation. These insights open up a new dimension for designing and producing metallic implants by considering the implant roughness to locally regulate osseointegration through coupling osteoclastogenesis with osteogenesis.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6213029 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Combinatorial Surface Roughness Effects on Osteoclastogenesis and Osteogenesis.

Zhang Yang Y Chen S Elisa SE Shao Jinlong J van den Beucken Jeroen J J P JJJP

ACS applied materials & interfaces 20181016 43

Implant surface properties are a key factor in bone responses to metallic bone implants. In view of the emerging evidence on the important role of osteoclasts in bone regeneration, we here studied how surface roughness affects osteoclastic differentiation and to what extent these osteoclasts have stimulatory effects on osteogenic differentiation of osteoprogenitor cells. For this, we induced osteoclasts derived from RAW264.7 cell line and primary mouse macrophages on titanium surfaces with diffe ...[more]

PMID: 30270615

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Project description:Osteogenesis and osteoclastogenesis are closely associated during the bone regeneration process. The development of multifunctional bone repair scaffolds with dual therapeutic actions (pro-osteogenesis and anti-osteoclastogenesis) is still a challenging task for bone tissue engineering applications. Herein, through a facile surface coating process, mussel-inspired polydopamine (PDA) is adhered to the surface of a biocompatible porous scaffold followed by the immobilization of a small-molecule activator (LYN-1604 (LYN)) and the subsequent in situ coprecipitation of hydroxyapatite (HA) nanocrystals. PDA, acting as an intermediate bridge, can provide strong LYN immobilization and biomineralization ability, while LYN targets osteoclast precursor cells to inhibit osteoclastic differentiation and functional activity, which endows LYN/HA-coated hybrid scaffolds with robust anti-osteoclastogenesis ability. Due to the synergistic effects of the LYN and HA components, the obtained three-dimensional hybrid scaffolds exhibited the dual effects of osteoclastic inhibition and osteogenic stimulation, thereby promoting bone tissue repair. Systematic characterization experiments confirmed the successful fabrication of LYN/HA-coated hybrid scaffolds, which exhibited an interconnected porous structure with nanoroughened surface topography, favorable hydrophilicity, and improved mechanical properties, as well as the sustained sequential release of LYN and Ca ions. In vitro experiments demonstrated that LYN/HA-coated hybrid scaffolds possessed satisfactory cytocompatibility, effectively promoting cell adhesion, spreading, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene and protein secretion, as well as stimulating angiogenic differentiation of endothelial cells. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity, F-actin ring staining, and osteoclastogenesis-related gene and protein secretion. More importantly, in a rat calvarial defect model, the newly developed hybrid scaffolds significantly promoted bone repair and regeneration. Microcomputed tomography, histological, and immunohistochemical analyses all revealed that the LYN/HA-coated hybrid scaffolds possessed not only reliable biosafety but also excellent osteogenesis-inducing and osteoclastogenesis-inhibiting effects, resulting in faster and higher-quality bone tissue regeneration. Taken together, this study offers a powerful and promising strategy to construct multifunctional nanocomposite scaffolds by promoting osteo/angiogenesis and suppressing osteoclastogenesis to accelerate bone regeneration.

Dataset Information

Combinatorial Surface Roughness Effects on Osteoclastogenesis and Osteogenesis.

Publications

Combinatorial Surface Roughness Effects on Osteoclastogenesis and Osteogenesis.

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