{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T07:11:33Z","timestamp":1767078693189,"version":"3.48.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteoclasts are bone\u2010resorbing cells, and understanding the pathways involved in osteoclast differentiation and activation is essential for developing treatments for bone diseases such as osteoporosis. Since osteoclast differentiation is regulated by signaling pathways such as Akt, MAPK, and NF\u2010\u03baB, it is important to identify their regulators. Makorin ring finger protein 1 (MKRN1), a conserved member of the ring finger protein family, is closely linked to the regulation of Akt and AMP\u2010activated protein kinase (AMPK), important signaling pathways in osteoclastogenesis. However, its specific role in osteoclasts has not been revealed.\n                    <jats:italic>Mkrn1<\/jats:italic>\n                    was overexpressed using a retrovirus or silenced using small interfering RNA (siRNA) in bone marrow\u2010derived macrophages (BMMs). Subsequently, osteoclast differentiation was induced using receptor activator of nuclear factor kappa B (NF\u2010\u03baB) ligand (RANKL) and assessed via tartrate\u2010resistant acid phosphatase (TRAP) staining. Additionally, the role of Mkrn1 in osteoclastogenesis was confirmed using\n                    <jats:italic>Mkrn1<\/jats:italic>\n                    \u2010deficient cells. Western blot analysis was employed to evaluate Mkrn1\u2010associated Akt and AMPK activation. The bone phenotype of\n                    <jats:italic>Mkrn1<\/jats:italic>\n                    \u2010deficient mice was investigated through bone analysis. This study revealed that Mkrn1 significantly influences RANKL\u2010induced osteoclastogenesis. Overexpression of\n                    <jats:italic>Mkrn1<\/jats:italic>\n                    in BMMs enhanced osteoclast differentiation by promoting Akt phosphorylation and inhibiting AMPK phosphorylation upon RANKL stimulation. Conversely, siRNA\u2010mediated downregulation of MKRN1 reduced Akt phosphorylation and increased AMPK phosphorylation, impairing osteoclastogenesis. Furthermore, in vivo studies using\n                    <jats:italic>Mkrn1<\/jats:italic>\n                    knockout mice revealed a phenotype with increased bone volume. Our findings establish Mkrn1 as a positive regulator of osteoclast differentiation, highlighting its potential as a therapeutic target for bone diseases characterized by excessive bone resorption.\n                  <\/jats:p>","DOI":"10.1002\/jcp.70129","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:40:55Z","timestamp":1766990455000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MKRN1 Regulates RANKL\u2010Induced Differentiation Via Akt and AMPK Pathways"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-1499","authenticated-orcid":false,"given":"Inyoung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology Chonnam National University Medical School Gwangju Republic of Korea"},{"name":"Hard\u2010Tissue Biointerface Research Center, School of Dentistry Chonnam National University Gwangju Republic 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