{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:26:01Z","timestamp":1771460761111,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation (FAPESP\u2014S\u00e3o Paulo Research Foundation, S\u00e3o Paulo, SP, Brazil)","award":["2015\/50040-4"],"award-info":[{"award-number":["2015\/50040-4"]}]},{"name":"S\u00e3o Paulo Research Foundation (FAPESP\u2014S\u00e3o Paulo Research Foundation, S\u00e3o Paulo, SP, Brazil)","award":["04021-001"],"award-info":[{"award-number":["04021-001"]}]},{"name":"Graduate Program in Structural and Functional Biology, Federal University of S\u00e3o Paulo, S\u00e3o Paulo","award":["2015\/50040-4"],"award-info":[{"award-number":["2015\/50040-4"]}]},{"name":"Graduate Program in Structural and Functional Biology, Federal University of S\u00e3o Paulo, S\u00e3o Paulo","award":["04021-001"],"award-info":[{"award-number":["04021-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>This study investigated the effects of Bothrops moojeni (B. moojeni) venom and its high- (HMM) and low-molecular mass (LMM) fractions on human osteoclast (OC) differentiation and function in vitro, aiming to identify novel therapeutics for bone disorders. Venom preparations were applied at 5 \u00b5g\/mL (crude venom and HMM) or 1 \u00b5g\/mL (LMM) from day 4 of peripheral blood mononuclear cell (PBMC) differentiation through terminal OC formation, enabling evaluation across early differentiation, fusion, and maturation stages. RNA sequencing revealed 7793 genes common to all experimental groups, with unique gene expression signatures of 149 (control), 221 (HMM), 248 (crude venom), and 60 (LMM) genes, reflecting distinct molecular responses. The negative control PBMC group exhibited 1013 unique genes enriched in immune-related pathways, consistent with their undifferentiated state. Crude venom induced the broadest transcriptional modulation, upregulating key fusion (CD47) and resorption (CTSK) genes, and altering markers of OC differentiation. The HMM fraction predominantly influenced inflammatory and osteoclastogenic pathways, notably TNF and NF-\u03baB signaling, while the LMM fraction selectively regulated fusion-related genes (e.g., CD44) and immune pathways, indicating targeted modulation of OC activity. Cytokine profiling showed that crude venom and HMM suppressed osteoclastogenic cytokines such as IL-1\u03b2 and IL-6, supporting their potential use in inflammatory bone diseases. Pathway enrichment analyses confirmed these differential effects on immune response and bone resorption mechanisms. Together, these results demonstrate that B. moojeni venom and its fractions differentially impact OC biology, with crude venom exerting broad effects and HMM and LMM fractions offering more specific modulation. Future studies will isolate bioactive components and assess therapeutic efficacy in animal models of osteoporosis and rheumatoid arthritis.<\/jats:p>","DOI":"10.3390\/toxins17070358","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T08:47:14Z","timestamp":1753087634000},"page":"358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive RNA-Seq Analysis of Human Osteoclast Function in Response to Bothrops moojeni Venom Fractions: Pathways of Bone Resorption and Cytoskeletal Disruption"],"prefix":"10.3390","volume":"17","author":[{"given":"Fernanda","family":"D\u2019Am\u00e9lio","sequence":"first","affiliation":[{"name":"Postgraduate Program in Structural and Functional Biology, UNIFESP, S\u00e3o Paulo 04023-062, Brazil"},{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Laboratory of Genetics, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8197-2260","authenticated-orcid":false,"given":"Hugo","family":"Vigerelli","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-2577","authenticated-orcid":false,"given":"Rodrigo Pinheiro","family":"Araldi","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7398-4184","authenticated-orcid":false,"given":"Isabel de F\u00e1tima Correia","family":"Batista","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2406-0860","authenticated-orcid":false,"given":"Daniel Carvalho","family":"Pimenta","sequence":"additional","affiliation":[{"name":"Laboratory of Ecology and Evolution, Butantan Institute, S\u00e3o Paulo, 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Kerkis","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"},{"name":"Laboratory of Genetics, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,19]]},"reference":[{"key":"ref_1","first-page":"e10631","article-title":"Interspecies Single-Cell RNA-Seq Analysis Reveals the Novel Trajectory of Osteoclast Differentiation and Therapeutic Targets","volume":"6","author":"Omata","year":"2022","journal-title":"J. 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