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Sclerostin antibody corrects periodontal disease in type 2 diabetic mice
Hakan Turkkahraman, Shannan Flanagan, Tianli Zhu, Nisreen Akel, Silvia Marino, Dayane Ortega-Gonzalez, Xue Yuan, Teresita Bellido
Hakan Turkkahraman, Shannan Flanagan, Tianli Zhu, Nisreen Akel, Silvia Marino, Dayane Ortega-Gonzalez, Xue Yuan, Teresita Bellido
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Research Article Bone biology Inflammation

Sclerostin antibody corrects periodontal disease in type 2 diabetic mice

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Abstract

Type 2 diabetes (T2D) is on the rise worldwide and is associated with various complications in the oral cavity. Using an adult-onset diabetes preclinical model, we demonstrated profound periodontal alterations in T2D mice, including inflamed gingiva, disintegrated periodontal ligaments (PDLs), marked alveolar bone loss, and unbalanced bone remodeling due to decreased formation and increased resorption. Notably, we observed elevated levels of the Wnt signaling inhibitor sclerostin in the alveolar bone of T2D mice. Motivated by these findings, we investigated whether a sclerostin-neutralizing antibody (Scl-Ab) could rescue the compromised periodontium in T2D mice. Administering Scl-Ab subcutaneously once a week for 4 weeks, starting 4 weeks after T2D induction, led to substantial increases in bone mass. This effect was attributed to the inhibition of osteoclasts and promotion of osteoblasts in both control and T2D mice, effectively reversing the bone loss caused by T2D. Furthermore, Scl-Ab stimulated PDL cell proliferation, partially restored the PDL fibers, and mitigated inflammation in the periodontium. Our study thus established a T2D-induced periodontitis mouse model characterized by inflammation and tissue degeneration. Scl-Ab emerged as a promising intervention to counteract the detrimental effects of T2D on the periodontium, exhibiting limited side effects on other craniofacial hard tissues.

Authors

Hakan Turkkahraman, Shannan Flanagan, Tianli Zhu, Nisreen Akel, Silvia Marino, Dayane Ortega-Gonzalez, Xue Yuan, Teresita Bellido

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Figure 1

T2D mice displayed elevated gingival inflammation and PDL degeneration.

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T2D mice displayed elevated gingival inflammation and PDL degeneration.
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(A) Schematic of the study design. (B and C) H&E staining shows the gingiva. (D and E) Immunostaining of CD45. (F and G) Immunostaining of the neutrophil marker myeloperoxidase (MPO). The orange dotted lines indicate the boundary between the epithelium and the underlying lamina propria. (H and I) H&E staining shows the PDL. (J and K) Picrosirius red staining, viewed under polarized light. (L) Quantification of the Picrosirius red–positive PDL area (n = 8). *P < 0.01. (M and N) DAPI staining shows cells in the PDL. (O) Quantification of PDL cells from DAPI-stained slides (n = 8). *P < 0.001. (P and Q) Immunostaining of Ki67. (R) Quantification of Ki67+ PDL cells (n = 8). ns, not significant. (S and T) TUNEL staining shows cell apoptosis in the PDL. Yellow arrows indicate TUNEL+ apoptotic PDL cells. The white dashed lines indicate the boundary of PDL. The data were analyzed using the Student’s t test. Scale bar: 50 μm. LFD, low-fat diet; HFD, high-fat diet; STZ, streptozotocin; T2D, type 2 diabetes; Scl-Ab, sclerostin antibody; pdl, periodontal ligament; b, bone; d, dentin.

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