Effect of interleukin‐22 on osteogenic differentiation and the osteoclastogenic response of human periodontal ligament fibroblasts in vitro

Abstract

BackgroundInterleukin‐22 (IL‐22) exerts extensive biological effects, playing both protective and pathological roles in autoimmune and infectious diseases. However, the specific role and mechanism of IL‐22 in the pathogenesis of periodontitis have not been clarified. The aim of this study was to analyze the possible roles of IL‐22 in the osteoclastogenesis and osteogenesis of periodontitis.MethodsHuman periodontal ligament fibroblasts (hPDLFs) were treated with IL‐22 and/or lipopolysaccharide from Porphyromonas gingivalis (Pg‐LPS), and the mRNA and protein expression of RANKL and OPG were measured by qRT‐PCR and Western blotting, respectively. Western blotting was also used to examine the phosphorylated and total protein expression of MAPK signaling molecules. The role of the MAPK pathway in osteoclastogenesis marker expression was further confirmed by inhibition assays. For osteogenic assays, the mRNA expression of osteoblastic markers was quantified by qRT‐PCR, the alkaline phosphatase (ALP) activity of hPDLFs was measured by an ALP assay, and the mineralized nodules formed by hPDLFs were determined by Alizarin Red S staining.ResultsIL‐22 promoted the expression of RANKL in hPDLFs via the MAPK signaling pathway and further upregulated RANKL expression together with Pg‐LPS via the p38 MAPK pathway. IL‐22 could enhance the ALP activity and mineralized nodule formation of hPDLFs in the early period of osteogenic induction, while exhibiting no profound effect on the expression of osteoblastic markers.ConclusionIL‐22 plays regulatory roles in bone homeostasis, and it is likely to contribute to osteoclastogenesis as a proinflammatory cytokine in the pathogenesis of periodontitis.

Biomimetic Hydroxyapatite Nanorods Promote Bone Regeneration via Accelerating Osteogenesis of BMSCs through T Cell-Derived IL-22

“…IL-22 has been reported to accelerate bone degradation in arthritis, , and IL-22-expressing T cells have been indicated to mediate alveolar bone resorption . On the contrary, it has been shown that IL-22 induces osteogenic differentiation of mesenchymal stem cells and periodontal ligament fibroblasts . Different disease models and different progenitor cells studied may have contributed to the inconsistency.…”

“…67 On the contrary, it has been shown that IL-22 induces osteogenic differentiation of mesenchymal stem cells 68 and periodontal ligament fibroblasts. 69 Different disease models and different progenitor cells studied may have contributed to the inconsistency. Analysis of our data showed that HAp-100 induced the largest increase of IL-22 and produced the best osteogenic impact in injured mouse mandibles, pointing to a positive role of IL-22 in bone regeneration.…”

O-Polysaccharide Plays a Major Role on the Virulence and Immunostimulatory Potential of Aggregatibacter actinomycetemcomitans During Periodontal Infection

“…In turn, Th22 lymphocytes have also been described as an osteoclastogenic T helper subset (54). Similar to IL-17, IL-22 can directly promote osteoclast differentiation (54) and induce RANKL expression in periodontal ligament fibroblasts (55). Our results showed that components of the periodontal immune cell compartment are able to detect changes in the structure of O-PS from the A. actinomycetemcomitans LPS, which resulted in the modification of the local immune response mediated by the Th1, Th17, and Th22 lymphocytes.…”

Immunomodulatory nanotherapeutic approaches for periodontal tissue regeneration

“…116 They established that the optimized HAp nanorods could result in a greater production of IL-22 from T cells, thereby inducing the osteogenic differentiation of BMSCs and PDLCs via the JAK/STAT3 pathway. 116,117…”