PMID- 36210640 OWN - NLM STAT- MEDLINE DCOM- 20230202 LR - 20230907 IS - 1365-2184 (Electronic) IS - 0960-7722 (Print) IS - 0960-7722 (Linking) VI - 56 IP - 2 DP - 2023 Feb TI - Periplaneta Americana extract inhibits osteoclastic differentiation in vitro. PG - e13341 LID - 10.1111/cpr.13341 [doi] LID - e13341 AB - OBJECTIVES: Periplaneta americana extract (PAE) is proven to be promising in treating fever, wound healing, liver fibrosis, and cardiovascular disease. However, the role of PAE in skeletal disorders remains unclear. This study investigated whether PAE regulates osteoclastic differentiation in vitro via the culture using RAW264.7 cells and bone marrow derived macrophages (BMDMs). MATERIALS AND METHODS: RAW264.7 cells and BMDMs were cultured and induced for osteoclastic differentiation supplementing with different concentrations of PAE (0, 0.1, 1, and 10 mg/mL). Cell counting kit-8 (CCK-8) assay was used to detect the cytotoxicity and cell proliferation. TRAP staining, actin ring staining, real-time quantitative PCR (RT-qPCR), and bone resorption activity test were performed to detect osteoclastic differentiation. RT-qPCR and enzyme-linked immunosorbent assay (ELISA) were conducted to assay the expression and secretion of inflammatory factors. RNA sequencing (RNA-seq) and western blot analysis were carried out to uncover the underlying mechanism. RESULTS: CCK-8 results showed that 10 mg/mL and a lower concentration of PAE did not affect cell proliferation. RT-qPCR analysis verified that PAE down-regulated the osteoclastic genes Nfatc1, Ctsk, and Acp5 in macrophages. Moreover, PAE restrained the differentiation, formation, and function of osteoclasts. Besides, RT-qPCR and ELISA assays showed that PAE decreased inflammatory genes expression and reduced the secretion of inflammatory factors, including IL1beta, IL6, and TNFalpha. Subsequent RNA-seq analysis identified possible genes and signaling pathways of PAE-mediated osteoclastogenesis suppression. CONCLUSIONS: Our study indicates that PAE has inhibitive effects on osteoclastogenesis and may be a potential therapeutic alternative for bone diseases. CI - (c) 2022 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. FAU - Zhao, Bin AU - Zhao B AUID- ORCID: 0000-0003-4365-3821 AD - State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Zhang, Yuning AU - Zhang Y AD - State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Xu, Jie AU - Xu J AD - State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Li, Yuyu AU - Li Y AD - State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Yuan, Quan AU - Yuan Q AUID- ORCID: 0000-0002-2836-1081 AD - State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Zhou, Chenchen AU - Zhou C AUID- ORCID: 0000-0002-6427-5869 AD - State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China. LA - eng GR - 81901040/National Natural Science Foundation of China/ GR - 82171001/National Natural Science Foundation of China/ GR - 2020QNR00/Young Elite Scientist Sponsorship Program by CAST/ PT - Journal Article DEP - 20221009 PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 0 (RANK Ligand) SB - IM MH - Animals MH - *Periplaneta/metabolism MH - Osteoclasts/metabolism MH - Macrophages/metabolism MH - Osteogenesis/physiology MH - Cell Differentiation/physiology MH - RANK Ligand/metabolism PMC - PMC9890529 COIS- All authors declare that there is no conflict of interest. EDAT- 2022/10/11 06:00 MHDA- 2023/02/03 06:00 PMCR- 2022/10/09 CRDT- 2022/10/10 02:44 PHST- 2022/09/01 00:00 [revised] PHST- 2022/05/28 00:00 [received] PHST- 2022/09/07 00:00 [accepted] PHST- 2022/10/11 06:00 [pubmed] PHST- 2023/02/03 06:00 [medline] PHST- 2022/10/10 02:44 [entrez] PHST- 2022/10/09 00:00 [pmc-release] AID - CPR13341 [pii] AID - 10.1111/cpr.13341 [doi] PST - ppublish SO - Cell Prolif. 2023 Feb;56(2):e13341. doi: 10.1111/cpr.13341. Epub 2022 Oct 9.