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RESEARCH PRODUCT

Phytocystatin CsinCPI-2 Reduces Osteoclastogenesis and Alveolar Bone Loss

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Made available in DSpace on 2022-04-28T19:42:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-02-01 Periodontal disease (PD) is a polymicrobial chronic inflammatory condition of the supporting tissues around the teeth, leading to the destruction of surrounding connective tissue. During the progression of PD, osteoclasts play a crucial role in the resorption of alveolar bone that eventually leads to the loss of teeth if the PD is left untreated. Therefore, the development of antiresorptive therapies targeting bone-resorbing cells will significantly benefit the treatment of PD. Here, we demonstrate the inhibitory effect of CsinCPI-2, a novel cysteine peptidase inhibitor from the orange tree, on periodontitis-induced inflammation, alveolar bone loss, and osteoclast differentiation. Using the ligature-induced periodontitis model in mice, we show that treatment with CsinCPI-2 (0.8 µg/g of body weight) significantly reduced inflammatory cell infiltrate in the connective tissue and prevented the loss of alveolar bone mass (BV/TV) caused by PD, effects associated with diminished numbers of TRAP-positive multinucleated cells. Furthermore, CsinCPI-2 significantly downregulated the numbers of inflammatory cells expressing CD3, CD45, MAC387, and IL-1β. In vitro, CsinCPI-2 inhibited RANKL-induced TRAP+ multinucleated osteoclast formation in mouse bone marrow macrophage cultures in a concentration-dependent manner. This effect was not due to cytotoxicity, as demonstrated by the MTT assay. CsinCPI-2 inhibited RANKL-induced mRNA expression of Acp5, Calcr, and Ctsk, as well as the RANKL-induced upregulation of Nfatc1, a crucial transcription factor for osteoclast differentiation. Based on our findings, CsinCPI-2 prevents bone loss induced by PD by controlling the inflammatory process and acting directly on osteoclastogenesis, suggesting an interesting potential for CsinCPI-2 in the strategy for PD treatment. Department of Diagnosis and Surgery School of Dentistry São Paulo State University–UNESP Department of Periodontology and Operative Dentistry University Medical Center of the Johannes Gutenberg University Department of Genetics and Evolution Federal University of Sao Carlos Department of Morphology Genetics Orthodontics and Pediatric Dentistry São Paulo State University–UNESP Centre for Bone and Arthritis Research Department of Internal Medicine and Clinical Nutrition Institute for Medicine Sahlgrenska Academy University of Gothenburg Innovation in Biomaterials Laboratory Faculty of Dentistry Federal University of Goiás Department of Diagnosis and Surgery School of Dentistry São Paulo State University–UNESP Department of Morphology Genetics Orthodontics and Pediatric Dentistry São Paulo State University–UNESP