論文 - 詳細
| RRC ID | 78665 |
|---|---|
| 著者 | Iwata T, Kaneda-Ikeda E, Takahashi K, Takeda K, Nagahara T, Kajiya M, Sasaki S, Ishida S, Yoshioka M, Matsuda S, Ouhara K, Fujita T, Kurihara H, Mizuno N. |
| タイトル | Regulation of osteogenesis in bone marrow-derived mesenchymal stem cells via histone deacetylase 1 and 2 co-cultured with human gingival fibroblasts and periodontal ligament cells. |
| ジャーナル | J Periodontal Res |
| Abstract |
OBJECTIVE:This study aimed to determine the regulatory mechanism of bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation mediated by humoral factors derived from human periodontal ligament (HPL) cells and human gingival fibroblasts (HGFs). We analyzed histone deacetylase (HDAC) expression and activity involved in BM-MSC differentiation and determined their regulatory effects in co-cultures of BM-MSCs with HPL cells or HGFs. BACKGROUND:BM-MSCs can differentiate into various cell types and can, thus, be used in periodontal regenerative therapy. However, the mechanism underlying their differentiation remains unclear. Transplanted BM-MSCs are affected by periodontal cells via direct contact or secretion of humoral factors. Therefore, their activity is regulated by humoral factors derived from HPL cells or HGFs. METHODS:BM-MSCs were indirectly co-cultured with HPL cells or HGFs under osteogenic or growth conditions and then analyzed for osteogenesis, HDAC1 and HDAC2 expression and activity, and histone H3 acetylation. BM-MSCs were treated with trichostatin A, or their HDAC1 or HDAC2 expression was silenced or overexpressed during osteogenesis. Subsequently, they were evaluated for osteogenesis or the effects of HDAC activity. RESULTS:BM-MSCs co-cultured with HPL cells or HGFs showed suppressed osteogenesis, HDAC1 and HDAC2 expression, and HDAC phosphorylation; however, histone H3 acetylation was enhanced. Trichostatin A treatment remarkably suppressed osteogenesis, decreasing HDAC expression and enhancing histone H3 acetylation. HDAC1 and HDAC2 silencing negatively regulated osteogenesis in BM-MSCs to the same extent as that achieved by indirect co-culture with HPL cells or HGFs. Conversely, their overexpression positively regulated osteogenesis in BM-MSCs. CONCLUSION:The suppressive effects of HPL cells and HGFs on BM-MSC osteogenesis were regulated by HDAC expression and histone H3 acetylation to a greater extent than that mediated by HDAC activity. Therefore, regulation of HDAC expression has prospects in clinical applications for effective periodontal regeneration, mainly, bone regeneration. |
| 巻・号 | 58(1) |
| ページ | 83-96 |
| 公開日 | 2023-2-1 |
| DOI | 10.1111/jre.13070 |
| PMID | 36346011 |
| MeSH | Bone Marrow / metabolism Cell Differentiation Cells, Cultured Coculture Techniques Fibroblasts / metabolism Histone Deacetylase 1 / metabolism Histone Deacetylase 1 / pharmacology Histones / metabolism Humans Mesenchymal Stem Cells* Osteogenesis* Periodontal Ligament |
| リソース情報 | |
| ヒト・動物細胞 | MSCs |