2. Academic Validation
  3. Inhibition of PKM2 suppresses osteoclastogenesis and alleviates bone loss in mouse periodontitis

Inhibition of PKM2 suppresses osteoclastogenesis and alleviates bone loss in mouse periodontitis

  • Int Immunopharmacol. 2024 Feb 14:129:111658. doi: 10.1016/j.intimp.2024.111658.
Feng Li 1,  Xinyuan Liu 2,  Mingjuan Li 3,  Shuxuan Wu 4,  Yushi Le 5,  Jingjing Tan 6,  Chongjie Zhu 7,  Qilong Wan 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China. Electronic address: Leefeng@whu.edu.cn.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China. Electronic address: Xinyuanliu@whu.edu.cn.
  • 3 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China. Electronic address: Limingjuan@whu.edu.cn.
  • 4 Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China. Electronic address: shuxuann@connect.hku.hk.
  • 5 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China. Electronic address: leyushi@whu.edu.cn.
  • 6 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China. Electronic address: niannsuis@whu.edu.cn.
  • 7 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China. Electronic address: zhuchongjie@whu.edu.cn.
  • 8 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, China. Electronic address: qilong.wan@whu.edu.cn.
PMID: 38359663 DOI: 10.1016/j.intimp.2024.111658
Abstract

Background: Chronic periodontitis triggers an increase in osteoclastogenesis, with glycolysis playing a crucial role in this process. Pyruvate Kinase M2 (PKM2) is a critical Enzyme involved in glycolysis and pyruvate metabolism. Yet, the precise function of PKM2 in osteoclasts and their formation remains unclear and requires further investigation.

Methods: Bioinformatics was used to investigate critical biological processes in osteoclastogenesis. In vitro, osteoclastogenesis was analyzed using tartrate-resistant Acid Phosphatase (TRAP) staining, phalloidin staining, quantitative real‑time PCR (RT-qPCR), and Western blotting. Small interfering RNA (siRNA) of PKM2 and Shikonin, a specific inhibitor of PKM2, were used to verify the role of PKM2 in osteoclastogenesis. The mouse model of periodontitis was used to assess the effect of shikonin on bone loss. Analyses included micro computed tomography, immunohistochemistry, flow cytometry, TRAP staining and HE staining.

Results: Bioinformatic analysis revealed a significant impact of glycolysis and pyruvate metabolism on osteoclastogenesis. Inhibition of PKM2 leads to a significant reduction in osteoclastogenesis. In vitro, co-culture of the heat-killed Porphyromonas gingivalis significantly promoted osteoclastogenesis, concomitant with an increased PKM2 expression in osteoclasts. Shikonin weakened the promoting effect of porphyromonas gingivalis on osteoclastogenesis. In vivo experiments demonstrated that inhibition of PKM2 by shikonin alleviated bone loss induced by periodontitis, suppressed excessive osteoclastogenesis in alveolar bone, and reduced tissue inflammation to some extent.

Conclusion: PKM2 inhibition by shikonin, a specific inhibitor of this Enzyme, attenuated osteoclastogenesis and bone resorption in periodontitis. Shikonin appears to be a promising therapeutic agent for treating periodontitis.

Keywords

Glycolysis; Inflammation; M2 Type Pyruvate Kinase; Osteoclasts; Periodontitis.

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