2. Academic Validation
  3. Galectin-8 involves in arthritic condylar bone loss via podoplanin/AKT/ERK axis-mediated inflammatory lymphangiogenesis

Galectin-8 involves in arthritic condylar bone loss via podoplanin/AKT/ERK axis-mediated inflammatory lymphangiogenesis

  • Osteoarthritis Cartilage. 2023 Jan 23;S1063-4584(23)00026-2. doi: 10.1016/j.joca.2023.01.008.
J Shi 1,  Y Chen 2,  W Zhao 3,  Y Chen 4,  Q Yang 5,  Z Zhao 6,  H Wang 7,  W Zhou 8,  W Sun 9
Affiliations

Affiliations

  • 1 Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China; Department of Temporomandibular Joint and Maxillofacial Pain, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 2 Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: [email protected].
  • 3 Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: [email protected].
  • 4 Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: [email protected].
  • 5 Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: [email protected].
  • 6 Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: [email protected].
  • 7 Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: [email protected].
  • 8 Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China; Department of Temporomandibular Joint and Maxillofacial Pain, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
  • 9 Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: [email protected].
PMID: 36702375 DOI: 10.1016/j.joca.2023.01.008
Abstract

Objective: The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. Galectin-8 (Gal-8) regulates pathological lymphangiogenesis but the effects of which on inflammation-related condylar bone loss in temporomandibular joint (TMJ) have not been well studied.

Design: We used TNFα-transgenic (TNFTG) mice and their wildtype (WT) littermates to compare their inflammatory phenotype in TMJs. Next, lymphatic endothelial cells (LECs) were used to examine the effects of which on osteoclast formation, pro-inflammatory factor expression, and inflammatory lymphangiogenesis with or without thiodigalactoside (TDG, a Gal-8 inhibitor) treatment. At last, two murine models (TNFTG arthritic model and forced mouth opening model) were used to explore TDG as a potential drug for the treatment of inflammation-related condylar bone loss.

Results: In comparison to WT mice, lymphatic areas of lymphatic vessel endothelial receptor 1 (LYVE1)+/podoplanin (PDPN)+ and Gal-8+/PDPN+, TRAP-positive osteoclast number, and condylar bone loss are increased in TNFTG mice. Inhibition of Gal-8 in LECs by TDG, reduces TNFα-induced osteoclast formation, pro-inflammatory factor expression, and inflammatory lymphangiogenesis. In addition, Gal-8 promotes TNFα-activated Akt/ERK/NF-κB pathways by binding to PDPN. Finally, the administration of TDG attenuates inflammatory lymphangiogenesis, inhibits osteoclast activity, and reduces condylar bone loss in TNFTG arthritic mice and forced mouth opening mice.

Conclusions: Our findings reveal the important role of Gal-8-promoted pathological lymphangiogenesis in inflammation-related condylar bone loss.

Keywords

Condylar bone loss; Galectin-8; Lymphangiogenesis; Lymphatic endothelial cell; Osteoclast.

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