Ask about this productRelated genes to: RANKL protein
- Gene:
- TNFSF11 NIH gene
- Name:
- TNF superfamily member 11
- Previous symbol:
- -
- Synonyms:
- TRANCE, RANKL, OPGL, ODF, CD254
- Chromosome:
- 13q14
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-04
- Date modifiied:
- 2017-03-02
Related products to: RANKL protein
Related articles to: RANKL protein
- Bone metastasis remains a major cause of morbidity in estrogen receptor-positive breast cancer, with RANKL inhibitor resistance emerging as a critical clinical challenge. Nearly 40% of patients develop progressive skeletal lesions despite denosumab therapy, highlighting an urgent need to identify resistance mechanisms and alternative therapeutic strategies. We identified a RANKL-independent osteoclast activation pathway mediated by the CRKL/circCCDC50/NFATc1 axis. Mechanistically, CRKL promoted EIF4A3-dependent circCCDC50 biogenesis, which was packaged into large oncosomes and transferred to osteoclast precursors. Nuclear circCCDC50 recruited CARM1 to epigenetically activate NFATc1 transcription, establishing a self-reinforcing loop that sustained osteolysis despite RANKL blockade. Pharmacological inhibition of CARM1 (TP-064) effectively suppressed osteoclastogenesis and bone metastasis in denosumab-resistant models. These findings revealed a targetable resistance mechanism and provided a clinically actionable strategy to overcome microenvironment-driven metastasis through dual targeting of tumor and bone niches. - Source: PubMed
Publication date: 2026/05/15
Lin QunLuo JinpengDuan ZhuxiLuo JieerZhang WeiXia YuanZeng YinduoFang XiaolinLiang JiahuiChen JiayiLin QianchongQuan YilinHu RuiyuLiu HongcaiLiu QiangLi JunGong Chang - The increasing prevalence of bone-related diseases and the desire to improve patient outcomes are driving research into bone replacement materials that overcome the limits of current bone substitutes. Molybdenum (Mo) is a promising candidate as an implant and degradable bone replacement material because it combines three key properties: mechanical strength, biocompatibility, and resorbability. However, little is known about the cellular mechanisms induced by Mo on bone regeneration. This study exposed a complex in vitro bone model as quadruple culture with primary human osteoblasts, osteocytes, osteoclasts, and endothelial cells, to Mo powder extracts to understand cell-material interactions in a multicellular system. Extracts with a final concentration of 1 mM Mo in quadruple cultures induced osteogenic differentiation by stimulation of gene expression and ALP activity, and gene expression, as well as enhanced calcium deposition of osteoblasts. Furthermore, expression of osteoblasts increased significantly and network formation of HUVEC with stimulated expression occurred. However, CD31 () expression and endothelial network density were reduced, indicating a complex, mixed angiogenic response. In contrast, Mo inhibited osteoclast formation and slowed down osteocyte differentiation, reducing , , and gene expression. Additionally, the RANKL ()/OPG () ratio of osteocytes was shifted toward OPG after Mo treatment. Cellular effects are most likely caused by the presence of molybdate anions. In summary, Mo extracts stimulated early bone healing factors involved in osteogenesis, vascularization, and mineralization, while osteoclastogenesis was inhibited. These dual effects in vitro provide mechanistic evidence supporting the potential of Mo as a growth factor-free bone replacement material and establish a cellular foundation for further preclinical development. - Source: PubMed
Publication date: 2026/05/07
Wirsig KatharinaBernhardt Anne - Human periodontal ligament fibroblasts (PDLFs) can acquire osteoblast-like characteristics within periodontal lesions and contribute to osteoclastogenesis through the expression of receptor activator of nuclear factor (NF) κB ligand (RANKL). However, the microbial and cellular conditions required for RANKL induction remain unclear. This study compared the microbial responsiveness of undifferentiated and osteoblast-like PDLFs to clarify the mechanisms regulating RANKL expression. - Source: PubMed
Abe MasayoKamijyo KoheiOda ShintaroSakagami HiroshiHayashi JoichiroInomata Megumi - Altered glial function, and increased proinflammatory cytokines are associated with behavioral and cognitive problems seen in autism spectrum disorder (ASD). In this study, we aimed to investigate the neuroinflammatory process in ASD and the relationship between neuroinflammatory markers and the severity of autism symptoms. - Source: PubMed
Kara BülentSavaş MerveÖzer TolgahanŞişmanlar Şahika GülenAkarsu RemziyeÖztürk Sinem YavuzAkpinar Şeyma NurDeniz AdnanGüneş Ayfer SakaryaDursun FulyaAkkoyunlu Deniz SünnetçiÇine NaciTüzün Erdem - The objective of this study was to evaluate the effects of fermented soy extract (FSE) on bone metabolism and neuroendocrine regulation in an ovariectomized (OVX) mouse model of postmenopausal conditions. FSE administration improved bone microarchitecture and modulated key markers associated with bone turnover, including reduced CTX-1 and RANKL levels and increased OPG expression, indicating suppression of osteoclastogenesis. In addition, FSE enhanced estrogen receptor-related activity and upregulated genes involved in bone metabolism. Notably, FSE also increased estradiol, serotonin, and norepinephrine levels, suggesting a beneficial role in neuroendocrine regulation. Collectively, these findings indicate that FSE may serve as a promising natural intervention for alleviating postmenopausal bone loss and neuroendocrine imbalance, supporting its potential application in functional nutrition. - Source: PubMed
Chandimali NisansalaBak Seon GyeongHong Seong-MinHwang Ji YoungKwon Hyuck SeBae JaehoonCheong Sun HeeLee Seung-Jae