Flufenamic acid reduces alveolar bone loss and pyrazole 3 enhances alveolar bone recovery in periodontitis mice

Transient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes. To investigate the effects of TRPC6 activator, flufenamic acid (FFA), and TRPC3 inhibitor, pyrazole 3 (PYR), in human periodontal ligament (hPDL) cells and periodontitis mice. T...

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Published inJournal of veterinary science (Suwŏn-si, Korea) Vol. 26; no. 4; pp. e47 - 0
Main Authors Kim, Ae Ri, Kim, Aeryun, Yang, Yu-Mi, Yoo, Yun-Jung, Bak, Eun-Jung
Format Journal Article
LanguageEnglish
Published Korea (South) The Korean Society of Veterinary Science 01.07.2025
대한수의학회
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ISSN1229-845X
1976-555X
1976-555X
DOI10.4142/jvs.24344

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Abstract Transient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes. To investigate the effects of TRPC6 activator, flufenamic acid (FFA), and TRPC3 inhibitor, pyrazole 3 (PYR), in human periodontal ligament (hPDL) cells and periodontitis mice. The effects of FFA and PYR on osteoblastogenesis were evaluated in hPDL cells. To investigate periodontitis induction, mice were randomized to control (C), periodontitis (P), and FFA-treated periodontitis (P+FFA) groups. To investigate periodontitis recovery, mice were randomized to day 0 C (D0C), D0P, D3P, D3P+PYR, D7P, and D7P+PYR groups. Alveolar bone (AB) area, osteoclast formation, osteoid area, and Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor-κB ligand (RANKL) expression were evaluated. AB area was greater in the P+FFA group than in the P group, whereas the number of osteoclasts and RANKL expression were lower. AB and osteoid areas were larger in the D7P+PYR group than in the D7P group. RUNX2-positive osteoblasts were elevated in the D3P+PYR group compared to the D0C and D0P groups. Osteocalcin expression was significantly greater on D28 of osteoblast differentiation in hPDL cells in the PYR group compared to the differentiation group. These results suggest that FFA attenuates AB loss by inhibiting RANKL expression and osteoclast formation and that PYR contributes to AB recovery by enhancing new bone formation.
AbstractList Transient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes. To investigate the effects of TRPC6 activator, flufenamic acid (FFA), and TRPC3 inhibitor, pyrazole 3 (PYR), in human periodontal ligament (hPDL) cells and periodontitis mice. The effects of FFA and PYR on osteoblastogenesis were evaluated in hPDL cells. To investigate periodontitis induction, mice were randomized to control (C), periodontitis (P), and FFA-treated periodontitis (P+FFA) groups. To investigate periodontitis recovery, mice were randomized to day 0 C (D0C), D0P, D3P, D3P+PYR, D7P, and D7P+PYR groups. Alveolar bone (AB) area, osteoclast formation, osteoid area, and Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor-κB ligand (RANKL) expression were evaluated. AB area was greater in the P+FFA group than in the P group, whereas the number of osteoclasts and RANKL expression were lower. AB and osteoid areas were larger in the D7P+PYR group than in the D7P group. RUNX2-positive osteoblasts were elevated in the D3P+PYR group compared to the D0C and D0P groups. Osteocalcin expression was significantly greater on D28 of osteoblast differentiation in hPDL cells in the PYR group compared to the differentiation group. These results suggest that FFA attenuates AB loss by inhibiting RANKL expression and osteoclast formation and that PYR contributes to AB recovery by enhancing new bone formation.
Transient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes.IMPORTANCETransient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes.To investigate the effects of TRPC6 activator, flufenamic acid (FFA), and TRPC3 inhibitor, pyrazole 3 (PYR), in human periodontal ligament (hPDL) cells and periodontitis mice.OBJECTIVETo investigate the effects of TRPC6 activator, flufenamic acid (FFA), and TRPC3 inhibitor, pyrazole 3 (PYR), in human periodontal ligament (hPDL) cells and periodontitis mice.The effects of FFA and PYR on osteoblastogenesis were evaluated in hPDL cells. To investigate periodontitis induction, mice were randomized to control (C), periodontitis (P), and FFA-treated periodontitis (P+FFA) groups. To investigate periodontitis recovery, mice were randomized to day 0 C (D0C), D0P, D3P, D3P+PYR, D7P, and D7P+PYR groups. Alveolar bone (AB) area, osteoclast formation, osteoid area, and Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor-κB ligand (RANKL) expression were evaluated.METHODSThe effects of FFA and PYR on osteoblastogenesis were evaluated in hPDL cells. To investigate periodontitis induction, mice were randomized to control (C), periodontitis (P), and FFA-treated periodontitis (P+FFA) groups. To investigate periodontitis recovery, mice were randomized to day 0 C (D0C), D0P, D3P, D3P+PYR, D7P, and D7P+PYR groups. Alveolar bone (AB) area, osteoclast formation, osteoid area, and Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor-κB ligand (RANKL) expression were evaluated.AB area was greater in the P+FFA group than in the P group, whereas the number of osteoclasts and RANKL expression were lower. AB and osteoid areas were larger in the D7P+PYR group than in the D7P group. RUNX2-positive osteoblasts were elevated in the D3P+PYR group compared to the D0C and D0P groups. Osteocalcin expression was significantly greater on D28 of osteoblast differentiation in hPDL cells in the PYR group compared to the differentiation group.RESULTSAB area was greater in the P+FFA group than in the P group, whereas the number of osteoclasts and RANKL expression were lower. AB and osteoid areas were larger in the D7P+PYR group than in the D7P group. RUNX2-positive osteoblasts were elevated in the D3P+PYR group compared to the D0C and D0P groups. Osteocalcin expression was significantly greater on D28 of osteoblast differentiation in hPDL cells in the PYR group compared to the differentiation group.These results suggest that FFA attenuates AB loss by inhibiting RANKL expression and osteoclast formation and that PYR contributes to AB recovery by enhancing new bone formation.CONCLUSIONS AND RELEVANCEThese results suggest that FFA attenuates AB loss by inhibiting RANKL expression and osteoclast formation and that PYR contributes to AB recovery by enhancing new bone formation.
Importance: Transient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes. Objective: To investigate the effects of TRPC6 activator, flufenamic acid (FFA), and TRPC3 inhibitor, pyrazole 3 (PYR), in human periodontal ligament (hPDL) cells and periodontitis mice. Methods: The effects of FFA and PYR on osteoblastogenesis were evaluated in hPDL cells. To investigate periodontitis induction, mice were randomized to control (C), periodontitis (P), and FFA-treated periodontitis (P+FFA) groups. To investigate periodontitis recovery, mice were randomized to day 0 C (D0C), D0P, D3P, D3P+PYR, D7P, and D7P+PYR groups. Alveolar bone (AB) area, osteoclast formation, osteoid area, and Runt-related transcription factor 2 (RUNX2) and receptor activator of nuclear factor-κB ligand (RANKL) expression were evaluated. Results: AB area was greater in the P+FFA group than in the P group, whereas the number of osteoclasts and RANKL expression were lower. AB and osteoid areas were larger in the D7P+PYR group than in the D7P group. RUNX2-positive osteoblasts were elevated in the D3P+PYR group compared to the D0C and D0P groups. Osteocalcin expression was significantly greater on D28 of osteoblast differentiation in hPDL cells in the PYR group compared to the differentiation group. Conclusions and Relevance: These results suggest that FFA attenuates AB loss by inhibiting RANKL expression and osteoclast formation and that PYR contributes to AB recovery by enhancing new bone formation. KCI Citation Count: 0
Author Yang, Yu-Mi
Kim, Aeryun
Yoo, Yun-Jung
Bak, Eun-Jung
Kim, Ae Ri
AuthorAffiliation 3 Department of Dentistry, The Graduate School, Yonsei University, Seoul 03722, Korea
2 BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea
1 Department of Oral Biology, Yonsei University College of Dentistry, Seoul 03722, Korea
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Issue 4
Keywords Flufenamic acid
pyrazole
hPDL cells
periodontitis
Language English
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Current address: Department of Biomedical Science, HwaSung Medi-Science University, Hwaseong 18274, Korea.
These authors equally contributed to this work.
Current address: Oral Health Research Institute, Apple Tree Dental Hospital, Bucheon 14633, Korea.
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Snippet Transient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes. To investigate the effects of TRPC6...
Transient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes.IMPORTANCETransient receptor...
Importance: Transient receptor potential canonical 6 (TRPC6) and TRPC3 are involved in bone remodeling and other biological processes. Objective: To...
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SubjectTerms Alveolar Bone Loss - drug therapy
Animals
Flufenamic Acid - pharmacology
Flufenamic Acid - therapeutic use
Humans
Male
Mice
Mice, Inbred C57BL
Periodontal Ligament - cytology
Periodontal Ligament - drug effects
Periodontitis - drug therapy
Pyrazoles - pharmacology
Pyrazoles - therapeutic use
Research Report
수의학
Title Flufenamic acid reduces alveolar bone loss and pyrazole 3 enhances alveolar bone recovery in periodontitis mice
URI https://www.ncbi.nlm.nih.gov/pubmed/40765229
https://www.proquest.com/docview/3237002042
https://pubmed.ncbi.nlm.nih.gov/PMC12329063
https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART003230419
Volume 26
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