Force-Induced H2S by PDLSCs Modifies Osteoclastic Activity during Tooth Movement.
Hydrogen sulfide (H2S), a gasotransmitter, has been recently linked to mesenchymal stem cell (MSC) function and bone homeostasis. Periodontal ligament stem cells (PDLSCs) are the main MSCs in PDL, which respond to mechanical force to induce physiological activities during orthodontic tooth movement (OTM). However, it is unknown whether mechanical force might induce endogenous H2S production by PDLSCs to regulate alveolar bone homeostasis. Here, we used a mouse OTM model to demonstrate that orthodontic force-induced endogenous H2S production in PDL tissue was associated with macrophage accumulation and osteoclastic activity in alveolar bone. Then, we showed that mechanical force application induced cystathionine β-synthase (CBS) expression and endogenous H2S production by PDLSCs. Moreover, blocking endogenous H2S or systemically increasing H2S levels could decrease or enhance force-induced osteoclastic activities to control tooth movement. We further revealed how force-induced H2S production by PDLSCs contributed to the secretion of monocyte chemoattractant protein-1 (MCP-1) and the expression of receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) system by PDLSCs. The secretion and expression of these factors controlled macrophage migration and osteoclast differentiation. This study demonstrated that PDLSCs produced H2S to respond to and transduce force signals. Force-induced gasotransmitter H2S production in PDLSCs therefore regulated osteoclastic activities in alveolar bone and controlled the OTM process through the MCP-1 secretion and RANKL/OPG system.
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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Liu
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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Wen
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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He
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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Liu
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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Yang
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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Wang
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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Yan
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
Y
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Liu
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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Kou
1 Department of Orthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.|2 Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Haidian District, Beijing, P.R. China.
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Zhou
D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D002454:Cell Differentiation; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology*; D053244:Osteoprotegerin / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology*; D053245:RANK Ligand / Q000378:metabolism; D014087:Tooth Movement Techniques
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053244:Osteoprotegerin; D053245:RANK Ligand; D006862:Hydrogen Sulfide
bone remodeling; hydrogen sulfide; mechanical force; mesenchymal stem cells; orthodontic tooth movement; osteoclast