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Periodontitis is associated with significant alveolar bone loss. Patients with iron overload suffer more frequently from periodontitis, however, the underlying mechanisms remain largely elusive. Here, we investigated the role of transferrin receptor 2 (Tfr2), one of the main regulators of iron homeostasis, in the pathogenesis of periodontitis and the dental phenotype under basal conditions in mice. As Tfr2 suppresses osteoclastogenesis, we hypothesized that deficiency of Tfr2 may exacerbate periodontitis-induced bone loss. Mice lacking Tfr2 (Tfr2 -/- ) and wild-type (Tfr2 +/+ ) littermates were challenged with experimental periodontitis. Mandibles and maxillae were collected for microcomputed tomography and histology analyses. Osteoclast cultures from Tfr2 +/+ and Tfr2 -/- mice were established and analyzed for differentiation efficiency, by performing messenger RNA expression and protein signaling pathways. After 8 days, Tfr2-deficient mice revealed a more severe course of periodontitis paralleled by higher immune cell infiltration and a higher histological inflammation index than Tfr2 +/+ mice. Moreover, Tfr2-deficient mice lost more alveolar bone compared to Tfr2 +/+ littermates, an effect that was only partially iron-dependent. Histological analysis revealed a higher number of osteoclasts in the alveolar bone of Tfr2-deficient mice. In line, Tfr2-deficient osteoclastic differentiation ex vivo was faster and more efficient as reflected by a higher number of osteoclasts, a higher expression of osteoclast markers, and an increased resorptive activity. Mechanistically, Tfr2-deficient osteoclasts showed a higher p38-MAPK signaling and inhibition of p38-MAPK signaling in Tfr2-deficient cells reverted osteoclast formation to Tfr2 +/+ levels. Taken together, our data indicate that Tfr2 modulates the inflammatory response in periodontitis thereby mitigating effects on alveolar bone loss., (© 2024 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)

Objective: To evaluate if 3 peptides derived from the cartilage oligomeric matrix protein (COMP), which wounded zones of cartilage secrete into synovial fluid, possess biological activity and might therefore be involved in the regulation of specific aspects of joint regeneration., Methods: The 3 peptides were produced by chemical synthesis and then tested in vitro for known functions of the COMP C-terminal domain from which they derive, and which are involved in osteoarthritis: transforming growth factor-β (TGF-β) signaling, vascular homeostasis, and inflammation. Results . None of the peptides affected the gene expression of COMP in osteochondral progenitor cells ( P > 0.05). We observed no effects on the vascularization potential of endothelial cells ( P > 0.05). In cultured synovium explants, no differences on the expression of catabolic enzymes or proinflammatory cytokines were found when peptides were added ( P > 0.05)., Discussion and Conclusions: The 3 peptides tested do not regulate TGF-β signaling, angiogenesis and vascular tube formation, or synovial inflammation in vitro and therefore most likely do not play a major role in the disease process.