Analysis of the function of Sp7 in osteoclastogenesis using osteoblast-specific Sp7 knockout mice

• Project/Area Number: 19K18946
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Nagasaki University
• Principal Investigator: KOMORI Hisato 長崎大学, 医歯薬学総合研究科(歯学系), 特任研究員 (80770411)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Sp7 / 破骨細胞 / 骨吸収 / 骨芽細胞 / 骨細胞 / アポトーシス

Outline of Research at the Start

Sp7は、SPファミリーに相同性を持つ転写因子である。Sp7 ノックアウト(ko) マウスでは、骨芽細胞の形質を獲得する以前に分化がブロックされて、骨形成が全く起こらない。すなわち、骨芽細胞分化に必須な転写因子である。Sp7 koマウスでは骨芽細胞が全く存在しないため、骨芽細胞へ分化後のSp7の機能を明らかにするためには、骨芽細胞に分化後にSp7 を欠失させたマウスが必要である。このマウスを作製し、骨芽細胞機能及び破骨細胞分化に対するSp7の機能を明らかにする

Outline of Final Research Achievements

To clarify the function of Sp7 after the differentiation into osteoblasts, we generated 2.3 kb Col1a1 promoter-GFP-Cre transgenic mice. Using these mice, we further generated osteoblast-specific Sp7-deficient mice. The trabecular bone was increased and cortical bones was reduced in micro-CT analysis, and the cortical bone was porous and many TRAP-positive osteoclasts were observed in the cortical bone in histological analysis. TUNEL-positive apoptotic osteocytes were increased in the cortical bone. Porous cortical bone was considered to be caused by the increase of osteocyte apoptosis, which enhances osteoclastogenesis.

Academic Significance and Societal Importance of the Research Achievements

Sp7は前骨芽細胞から骨芽細胞への分化に必須な転写因子である。しかし、骨芽細胞分化後の機能は、まだ明確になっていない。それは、これまで使われてきた骨芽細胞特異的に発現する2.3 kb Col1a1 Creトランスジェニックマウスの発現レベルが低く、明確な表現型を得にくかったことが原因と考えられる。我々は、新たに2.3 kb Col1a1 GFP-Creトランスジェニックマウスを作製し、Sp7を骨芽細胞特異的に欠失させ、骨細胞の生存におけるその重要性を明らかにした。

Research Products

• [Journal Article] Runx2 is essential for the transdifferentiation of chondrocytes into osteoblasts (2020)
  • Author(s): Xin Qin, Qing Jiang, Kenichi Nagano, Takeshi Moriishi, Toshihiro Miyazaki, Hisato Komori, Kosei Ito, Klaus von der Mark, Chiharu Sakane, Hitomi Kaneko, Toshihisa Komori
  • Journal Title: PLOS Genetics Volume: 16
  • NAID: 120006980742
  • Peer Reviewed / Open Access
• [Journal Article] Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass (2020)
  • Author(s): Moriishi Takeshi、Ozasa Ryosuke、Ishimoto Takuya、Nakano Takayoshi、Hasegawa Tomoka、Miyazaki Toshihiro、Liu Wenguang、Fukuyama Ryo、Wang Yuying、Komori Hisato、Qin Xin、Amizuka Norio、Komori Toshihisa
  • Journal Title: PLOS Genetics Volume: 16 Issue: 5 Pages: 1008586-1008586
  • DOI: 10.1371/journal.pgen.1008586
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of a Constitutively Active Form of Hck in Chondrocytes Activates Wnt and Hedgehog Signaling Pathways, and Induces Chondrocyte Proliferation in Mice (2020)
  • Author(s): Matsuura Viviane K. S. Kawata、Yoshida Carolina Andrea、Komori Hisato、Sakane Chiharu、Yamana Kei、Jiang Qing、Komori Toshihisa
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 8 Pages: 2682-2682
  • DOI: 10.3390/ijms21082682
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of a constitutively active from of Hck in chondrocytes activates Wnt and hedgehog signaling pathways, and induces chondrocyte proliferation in mice. (2020)
  • Author(s): Kawata-Matsukura V, Yoshida CA, Komori H, Sakane C, Yamana K, Jiang Q, Komori T
  • Journal Title: Int J Mol Sci. Volume: 21 Pages: 2682-2682
  • Peer Reviewed
• [Journal Article] Antxrl,which is a target of Runx2, regulates chondrocyte proliferation and apoptosis. (2020)
  • Author(s): Jiang Q, Qin X, Yoshida CA, Komori H, Yamana K, Ohba S, Hojo H, Croix BS, Kawata-Matsuura V, Komori T
  • Journal Title: Int J Mol Sci. Volume: 21 Pages: 2425-2425
  • Peer Reviewed