title: Polycan suppresses osteoclast differentiation and titanium particle-induced osteolysis in mice.
abstract: Particle-induced osteolysis is a major issue, and it is most likely the result of enhanced osteoclast activation in the pathogenesis of various skeletal diseases. This study investigated whether the inhibitory effect that Polycan has on osteoclast differentiation can be used to treat osteolysis induced by titanium (Ti) particles. To this end, the effects of Polycan were examined in terms of the cytotoxicity, osteoclast differentiation, cytokine expression, and Ti-induced calvarial osteolysis. Polycan had no significant cytotoxic effects on bone marrow macrophages (BMMs) but instead increased BMM proliferation. High levels of interleukin (IL)-6, IL-12, and macrophage colony-stimulating factor (M-CSF) were expressed in BMM cells in the presence of Polycan, suggesting that Polycan drives the differentiation of BMMs into M1 macrophages. Polycan significantly inhibited osteoclast differentiation induced by M-CSF and the receptor activator of nuclear factor kappa-B ligand (RANKL). The expression levels of the osteoclast marker genes significantly decreased, and Polycan induced and maintained the expression of IL-12, which suppressed osteoclast differentiation. In contrast, the RANKL signaling pathway was not inhibited by Polycan. An in vivo calvarial osteolysis model revealed that Polycan significantly decreased the osteoclast numbers and suppressed osteolysis. Our results suggest that the natural compound Polycan is a good candidate for therapeutic intervention against enhanced osteoclast differentiation and Ti particle-induced osteolysis. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1170-1175, 2016.
authors.affiliation: Department of Dental Hygiene, Daegu Health College, 15 Youngsong-Ro, Buk-Gu, 702-722, Daegu, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Lee
authors.affiliation: Department of Preventive Dentistry, School of Dentistry, Kyungpook National University, 2-188-1 Jung-Gu, Samduk-Dong, 700-412, Daegu, Republic of Korea.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Oral Pathology, School of Dentistry, Kyungpook National University, 2-188-1 Jung-Gu, Samduk-Dong, 700-412, Daegu, Republic of Korea.
authors.forename: Eui-Kyun
authors.initials: EK
authors.lastname: Park
authors.affiliation: Department of Preventive Dentistry, School of Dentistry, Kyungpook National University, 2-188-1 Jung-Gu, Samduk-Dong, 700-412, Daegu, Republic of Korea.
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Im
authors.affiliation: Department of Preventive Dentistry, School of Dentistry, Kyungpook National University, 2-188-1 Jung-Gu, Samduk-Dong, 700-412, Daegu, Republic of Korea.
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Preventive Dentistry, School of Dentistry, Kyungpook National University, 2-188-1 Jung-Gu, Samduk-Dong, 700-412, Daegu, Republic of Korea.
authors.forename: Keun-Bae
authors.initials: KB
authors.lastname: Song
mesh_terms: D000818:Animals; D001203:Ascomycota / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D062610:Fungal Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D014025:Titanium / Q000633:toxicity*
chemical_list: D016207:Cytokines; D062610:Fungal Polysaccharides; D014025:Titanium
keywords: Polycan; osteoclast differentiation; osteolysis; titanium