Attenuation of intervertebral disc degeneration and osteophyte formation via inhibition of Hedgehog signaling

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10952
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: NAKAMURA EIICHIRO 産業医科大学, 医学部, 准教授 (10412644)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 椎間板変性 / Hedgehog / Smoothened / 骨棘 / Sonidegib / 骨・軟骨代謝学 / Cre / 脊椎脊髄病

Outline of Final Research Achievements

We investigated whether inhibition of smoothened (Smo), a key component of hedgehog pathway in the process of endochondral ossification and intervertebral disc development, attenuates intervertebral disc degeneration in the degenerative spine model. Mice were intraperitoneally administered saline or Sonidegib, an antagonist of Smo, 3 times per week after operation for 10 weeks. Disc height reduction rate and Masuda classification score was significantly suppressed in Sonidegib group against the saline group at 10 weeks after operation. Saline group showed severe intervertebral disc degeneration, collapse of vertebral end plate layer, hypertrophic changes of chondrocytes in the vertebral end plate cartilage and osteophyte formation in the corner of vertebra. In contrast, all these phenomena were attenuated in the mice with administration of Sonidegib, indicating that hedgehog signaling has a crucial role in the degenerative spondylosis of spine.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

加齢に伴い椎間板変性が起こり腰痛や脊柱管狭窄、椎間不安定性、脊柱変形を引き起こし多くの脊椎疾患の原因となる。椎間板の発生や変性過程で発現するヘッジホグシグナルを伝達する膜蛋白のスムースンドの阻害薬であるソニデジブを椎間板変性モデルのマウスに腹腔内投与したところ、椎間板変性の抑制効果が見られた。ソニデジブは癌治療薬としてすでに臨床試験中の薬剤であり、超高齢社会で脊椎加齢変性疾患に対する抑制治療への応用が期待される。