Evaluating the oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol in periodontal regeneration using periodontal ligament stem cells and alveolar bone healing models

• Published in: Stem cell research & therapy Vol. 8; no. 1; p. 276
• Main Authors: Lee, Jin-Sun, Kim, EunJi, Han, Seonggu, Kang, Kyung Lhi, Heo, Jung Sun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.12.2017; BioMed Central; BMC
• Subjects: ABCA1 protein; Alkaline phosphatase; Alveolar bone; Alveolar bone defect; ATP-binding protein; Bone growth; Bone healing; Bone morphogenetic protein 2; Bone morphogenetic proteins; Bone regeneration; Calcium (intracellular); Cholesterol; Endocrinology; Gene expression; Gli1 protein; Growth factors; Hedgehog protein; Homeostasis; Ligaments; Liver X receptors; Metabolism; Mineralization; Nuclear receptors; Osteogenesis; Osteogenic differentiation; Oxysterol; Periodontal ligament; Periodontal ligament stem cells; Phosphatase; Phosphatases; Physiological aspects; Proteins; Regeneration; RNA; siRNA; Stem cells; Surgery; Teeth; Transfection; Periodontal ligament stem cells; Alveolar bone defect; Bone regeneration; Osteogenic differentiation; Oxysterol
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-017-0725-9

Oxysterols, oxygenated by-products of cholesterol biosynthesis, play roles in various physiological and pathological systems. However, the effects of oxysterols on periodontal regeneration are unknown. This study investigated the effects of the specific oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on the regeneration of periodontal tissues using in-vitro periodontal ligament stem cells (PDLSCs) and in-vivo models of alveolar bone defect. To evaluate the effects of the combined oxysterols on PDLSC biology, we studied the SS-induced osteogenic differentiation of PDLSCs by assessing alkaline phosphatase activity, intracellular calcium levels [Ca ] , matrix mineralization, and osteogenic marker mRNA expression and protein levels. To verify the effect of oxysterols on alveolar bone regeneration, we employed tooth extraction bone defect models. Oxysterols increased the osteogenic activity of PDLSCs compared with the control group. The expression of liver X receptor (LXR) α and β, the nuclear receptors for oxysterols, and their target gene, ATP-binding cassette transporter A1 (ABCA1), increased significantly during osteogenesis. Oxysterols also increased protein levels of the hedgehog (Hh) receptor Smo and the transcription factor Gli1. We further confirmed the reciprocal reaction between the LXRs and Hh signaling. Transfection of both LXRα and LXRβ siRNAs decreased Smo and Gli1 protein levels. In contrast, the inhibition of Hh signaling attenuated the LXRα and LXRβ protein levels. Subsequently, SS-induced osteogenic activity of PDLSCs was suppressed by the inhibition of LXRs or Hh signaling. The application of SS also enhanced bone formation in the defect sites of in-vivo models, showing equivalent efficacy to recombinant human bone morphogenetic protein-2. These findings suggest that a specific combination of oxysterols promoted periodontal regeneration by regulating PDLSC activity and alveolar bone regeneration.