TY - JOUR
T1 - Sonic hedgehog reduces alveolar bone resorption by triggering the coupling of type H vessel formation and osteogenesis in a periodontitis model
AU - Zhou, Huan
AU - Qi, Yan Xin
AU - Ma, Shao Yang
AU - Liu, Jin
AU - Zhu, Chun Hui
AU - Yu, Shu Chen
AU - Li, Ang
AU - Pei, Dan Dan
N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/12
Y1 - 2026/12
N2 - Background: Sonic hedgehog (Shh) has the dual function of promoting angiogenesis and osteogenesis, However, whether Shh treatment can accelerate alveolar bone regeneration by promoting the coupling of type H vessel formation and osteogenesis within periodontitis has not been verified. Methods: A series of angiogenesis-related assays (including cell counting kit-8, transwell migration, scratch wound healing, and tube formation) were established to explore the proliferation, migration, and tube formation abilities of endothelial cells (ECs) in response to Shh. Alizarin Red S staining and alkaline phosphatase activity assay were subsequently conducted to determine the effect of Shh on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Additionally, the expression levels of key factors of Slit3/Robo4/HIF-1α pathway, and angiogenesis- and osteogenesis-related genes/proteins were assessed. In addition, a mouse periodontitis model was employed, along with micro-CT and immunofluorescence staining analyses, to explore the effects of Shh administration on type H vessel formation and alveolar bone regeneration. Results: Shh treatment increased the proliferation, migration, tube formation and CD31&EMCN intensity of ECs, and enhanced the osteogenic differentiation potential of PDLSCs in vitro. Mechanism studies found Shh treatment up-regulated the expression levels of Slit3, Robo4 and HIF-1α in ECs. Besides, silencing of Slit3 reserved the promoted angiogenic activity of ECs in the presence of Shh, and significantly down-regulated the expression levels of Robo4 and HIF-1α. In vivo studies verified that Shh administration markedly promoted type H vessel formation, increased the proportion of HIF-1α staining cells, and eventually attenuated bone loss within periodontitis model. Conclusion: Shh administration accelerates type H vessel formation by the Slit3/Robo4/HIF-1α signaling, to further alleviate alveolar bone resorption within periodontitis.
AB - Background: Sonic hedgehog (Shh) has the dual function of promoting angiogenesis and osteogenesis, However, whether Shh treatment can accelerate alveolar bone regeneration by promoting the coupling of type H vessel formation and osteogenesis within periodontitis has not been verified. Methods: A series of angiogenesis-related assays (including cell counting kit-8, transwell migration, scratch wound healing, and tube formation) were established to explore the proliferation, migration, and tube formation abilities of endothelial cells (ECs) in response to Shh. Alizarin Red S staining and alkaline phosphatase activity assay were subsequently conducted to determine the effect of Shh on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Additionally, the expression levels of key factors of Slit3/Robo4/HIF-1α pathway, and angiogenesis- and osteogenesis-related genes/proteins were assessed. In addition, a mouse periodontitis model was employed, along with micro-CT and immunofluorescence staining analyses, to explore the effects of Shh administration on type H vessel formation and alveolar bone regeneration. Results: Shh treatment increased the proliferation, migration, tube formation and CD31&EMCN intensity of ECs, and enhanced the osteogenic differentiation potential of PDLSCs in vitro. Mechanism studies found Shh treatment up-regulated the expression levels of Slit3, Robo4 and HIF-1α in ECs. Besides, silencing of Slit3 reserved the promoted angiogenic activity of ECs in the presence of Shh, and significantly down-regulated the expression levels of Robo4 and HIF-1α. In vivo studies verified that Shh administration markedly promoted type H vessel formation, increased the proportion of HIF-1α staining cells, and eventually attenuated bone loss within periodontitis model. Conclusion: Shh administration accelerates type H vessel formation by the Slit3/Robo4/HIF-1α signaling, to further alleviate alveolar bone resorption within periodontitis.
KW - Bone resorption
KW - Periodontitis
KW - Sonic hedgehog
KW - Type H vessel
UR - https://www.scopus.com/pages/publications/105048221104
U2 - 10.1186/s12903-026-08637-4
DO - 10.1186/s12903-026-08637-4
M3 - 文章
C2 - 42192364
AN - SCOPUS:105048221104
SN - 1472-6831
VL - 26
JO - BMC Oral Health
JF - BMC Oral Health
IS - 1
M1 - 1582
ER -