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PLoS One. 2017 Aug 17;12(8):e0183359. doi: 10.1371/journal.pone.0183359. eCollection 2017.

Titanium biomaterials with complex surfaces induced aberrant peripheral circadian rhythms in bone marrow mesenchymal stromal cells.

Author information

1
Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California, United States of America.
2
Division of Oral Biology & Medicine, UCLA School of Dentistry, Los Angeles, California, United States of America.
3
Division of Advanced Prosthodontics, UCLA School of Dentistry, Los Angeles, California, United States of America.
4
Department of Oral Rehabilitation, Section of Oral Implantology, Fukuoka Dental College, Fukuoka, Japan.
5
Department of Conservative Dentistry, School of Dentistry Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
6
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
7
Division of Plastic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
8
Department of Psychiatry & Biobehavioral Science, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.

Abstract

Circadian rhythms maintain a high level of homeostasis through internal feed-forward and -backward regulation by core molecules. In this study, we report the highly unusual peripheral circadian rhythm of bone marrow mesenchymal stromal cells (BMSCs) induced by titanium-based biomaterials with complex surface modifications (Ti biomaterial) commonly used for dental and orthopedic implants. When cultured on Ti biomaterials, human BMSCs suppressed circadian PER1 expression patterns, while NPAS2 was uniquely upregulated. The Ti biomaterials, which reduced Per1 expression and upregulated Npas2, were further examined with BMSCs harvested from Per1::luc transgenic rats. Next, we addressed the regulatory relationship between Per1 and Npas2 using BMSCs from Npas2 knockout mice. The Npas2 knockout mutation did not rescue the Ti biomaterial-induced Per1 suppression and did not affect Per2, Per3, Bmal1 and Clock expression, suggesting that the Ti biomaterial-induced Npas2 overexpression was likely an independent phenomenon. Previously, vitamin D deficiency was reported to interfere with Ti biomaterial osseointegration. The present study demonstrated that vitamin D supplementation significantly increased Per1::luc expression in BMSCs, though the presence of Ti biomaterials only moderately affected the suppressed Per1::luc expression. Available in vivo microarray data from femurs exposed to Ti biomaterials in vitamin D-deficient rats were evaluated by weighted gene co-expression network analysis. A large co-expression network containing Npas2, Bmal1, and Vdr was observed to form with the Ti biomaterials, which was disintegrated by vitamin D deficiency. Thus, the aberrant BMSC peripheral circadian rhythm may be essential for the integration of Ti biomaterials into bone.

PMID:
28817668
PMCID:
PMC5560683
DOI:
10.1371/journal.pone.0183359
[Indexed for MEDLINE]
Free PMC Article

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