ArticleCell communication and signaling : CCS2024
IL13Rα2 as a crucial receptor for Chi3l1 in osteoclast differentiation and bone resorption through the MAPK/AKT pathway.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 53 citations in OpenAlex.
- Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.Annals of medicine · 2026Article
- Redefining CHI3L1: Therapeutic Opportunities at the Crossroads of Immune Suppression and Disease Progression.Medicinal research reviews · 2026Review
- Osteomyelitis: Epidemiology, Classification, Pathophysiology, Clinical Features, Diagnosis, and Management.MedComm · 2026Review
- ATM promotes bone metastatic propensity of breast cancer by inducing osteoclastogenesis via the NFκB-CCL2 pathway.Acta pharmacologica Sinica · 2026Article
- CHI3L1 Is Associated With TP53 Signaling and Promotes Papillary Thyroid Carcinoma Progression.Cancer reports (Hoboken, N.J.) · 2026Article
- Nanometer preparation of natural bioactive compounds for treatment of rheumatoid arthritis.Journal of pharmaceutical analysis · 2025Review
- Hydrothermal Magnesium Alloy Extracts Modulate MicroRNA Expression in RAW264.7 Cells: Implications for Bone Remodeling.Journal of functional biomaterials · 2025Article
- TRAF1 promotes osteoclastogenesis by enhancing metabolic adaptation to oxidative phosphorylation in an AKT-dependent manner.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Chitinase-3 Like-Protein-1 Signature in Neurological Disorders: Emphasis on Stroke.Journal of molecular neuroscience : MN · 2025Review
- Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications.Molecular neurodegeneration · 2025Review
- IL-13Rα2 Is Involved in Resistance to Doxorubicin and Survival of Osteosarcoma Patients.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Chitin-mediated blockade of chitinase-like proteins reduces tumor immunosuppression, inhibits lymphatic metastasis and enhances anti-PD-1 efficacy in complementary TNBC models.Breast cancer research : BCR · 2024Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrevious research has revealed that the 18 glycoside hydrolase gene family (GH18) member Chitinase 3-like 1 (Chi3l1) can regulate osteoclast differentiation and bone resorption. However, its downstream receptors and molecular mechanisms during osteoclastogenesis have yet to be elucidated.
methodsInitially, we conducted a comprehensive investigation to evaluate the effects of recombinant Chi3l1 protein or Chi3l1 siRNA on osteoclast differentiation and the RANKL-induced MAPK/AKT signaling pathways. Moreover, we used immunofluorescence and immunoprecipitation assays to identify IL13Rα2 as the downstream receptor of Chi3l1. Subsequently, we investigated the impact of IL13Rα2 recombinant protein or IL13Rα2-siRNA on osteoclast differentiation and the associated signaling pathways. Finally, we performed in vivo experiments to examine the effect of recombinant IL13Rα2 protein in an LPS-induced mouse model of cranial osteolysis.
resultsOur findings highlight that the administration of recombinant Chi3l1 protein increased the formation of osteoclasts and bolstered the expression of several osteoclast-specific genes (TRAP, NFATC1, CTR, CTSK, V-ATPase d2, and Dc-STAMP). Additionally, Chi3l1 significantly promoted the RANKL-induced MAPK (ERK/P38/JNK) and AKT pathway activation, whereas Chi3l1 silencing inhibited this process. Next, using immunofluorescence and co-immunoprecipitation assays, we identified IL13Rα2 as the binding partner of Chi3l1 during osteoclastogenesis. IL13Rα2 recombinant protein or IL13Rα2-siRNA also inhibited osteoclast differentiation, and IL13Rα2-siRNA attenuated the RANKL-induced activation of the MAPK (ERK/P38/JNK) and AKT pathways, similar to the effects observed upon silencing of Chi3l1. Moreover, the promoting effect of recombinant Chi3l1 protein on osteoclastogenesis and the activation of the MAPK and AKT pathways was reversed by IL13Rα2 siRNA. Finally, recombinant LI13Rα2 protein significantly attenuated the LPS-induced cranial osteolysis and the number of osteoclasts in vivo.
conclusionsOur findings suggested that IL13Rα2 served as a crucial receptor for Chi3l1, enhancing RANKL-induced MAPK and AKT activation to promote osteoclast differentiation. These findings provide valuable insights into the molecular mechanisms of Chi3l1 in osteoclastogenesis, with potential therapeutic implications for osteoclast-related diseases. Video Abstract.
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