Clec11a, also known as stem cell growth factor (SCGF), C-type lectin superfamily member 3 (CLECSF3), or osteolectin, is a sulfated glycoprotein [5]. It significantly promotes osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts, stimulates chondrocyte proliferation, and thus plays a crucial role in bone mass regulation [2]. It is also involved in regulating hematopoietic differentiation and homeostasis [5]. In bone, receptor ligand binding of Clec11a activates downstream signaling cascades like glycogen synthase kinase 3 (GSK3), β -catenin, and Wnt, resulting in the expression of osteoblast-related gene transcripts [5].

In osteoporosis mouse models, human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hucMSC-EVs) prevent bone loss and maintain bone strength by enhancing bone formation, reducing marrow fat accumulation, and decreasing bone resorption. This is achieved through the transfer of Clec11A, which enhances the shift from adipogenic to osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) and inhibits osteoclast formation [1]. In the context of bone construction and remodeling, Clec11a has high therapeutic potential for treating various bone diseases and can enhance the therapeutic effects of the parathyroid hormone against osteoporosis [2]. In addition, it is involved in the stress/adaptive response of bone to exercise via mechanical stimulation of the cation channel Pieoz1 [2]. In adipose tissue, cells marked by Clec11a expression are part of the adipocyte progenitor lineage hierarchy [4]. In diabetes research, exogenous recombinant human CLEC11A (rhCLEC11A) promotes insulin secretion, insulin content, and proliferation in human beta-cells, which are associated with the increased expression levels of transcription factors MAFA and PDX1 [3]. In acute myeloid leukemia (AML), high CLEC11A expression is linked with favorable prognosis, while its hypermethylation is associated with poor induction remission rate and dismal survival [7]. In gastric cancer, CLEC11A is over-expressed, and its elevated expression indicates an unfavorable prognosis. Suppressing its expression inhibits cell cycle progression, migration, and invasion, and affects the infiltration of immune cells [6,8].

In summary, Clec11a is a multi-functional gene with essential roles in bone metabolism, hematopoiesis, adipose tissue development, insulin-related functions, and in certain cancers. Studies using in vivo models such as osteoporosis mouse models have revealed its potential as a therapeutic target for bone diseases like osteoporosis. In cancer, its expression and methylation patterns have prognostic significance, suggesting its importance in understanding disease mechanisms and developing treatment strategies [1,2,6,7,8].

References:

1. Hu, Yin, Zhang, Yan, Ni, Chu-Yu, Luo, Juan, Xie, Hui. 2020. Human umbilical cord mesenchymal stromal cells-derived extracellular vesicles exert potent bone protective effects by CLEC11A-mediated regulation of bone metabolism. In Theranostics, 10, 2293-2308. doi:10.7150/thno.39238. https://pubmed.ncbi.nlm.nih.gov/32089743/

2. Xu, Ke, Huang, Rui-Qi, Wen, Ruiming, Cheng, Yang, Chang, Bo. 2024. The role of Clec11a in bone construction and remodeling. In Frontiers in endocrinology, 15, 1429567. doi:10.3389/fendo.2024.1429567. https://pubmed.ncbi.nlm.nih.gov/39188913/

3. Shi, Ruifeng, Cen, Jing, Westermark, Gunilla T, Sun, Zilin, Lau, Joey. 2023. CLEC11A improves insulin secretion and promotes cell proliferation in human beta-cells. In Journal of molecular endocrinology, 71, . doi:10.1530/JME-22-0066. https://pubmed.ncbi.nlm.nih.gov/37078556/

4. Merrick, David, Sakers, Alexander, Irgebay, Zhazira, Percec, Ivona, Seale, Patrick. . Identification of a mesenchymal progenitor cell hierarchy in adipose tissue. In Science (New York, N.Y.), 364, . doi:10.1126/science.aav2501. https://pubmed.ncbi.nlm.nih.gov/31023895/

5. Wang, Miao, Guo, Jianmin, Zhang, Lingli, Xu, Jiake, Zou, Jun. 2020. Molecular structure, expression, and functional role of Clec11a in skeletal biology and cancers. In Journal of cellular physiology, 235, 6357-6365. doi:10.1002/jcp.29600. https://pubmed.ncbi.nlm.nih.gov/32003015/

6. Zheng, Qing, Gong, Zhenqi, Li, Baizhi, Huang, Cong, Wang, Huaiming. 2024. Identification and characterization of CLEC11A and its derived immune signature in gastric cancer. In Frontiers in immunology, 15, 1324959. doi:10.3389/fimmu.2024.1324959. https://pubmed.ncbi.nlm.nih.gov/38348052/

7. Yin, Chengliang, Zhang, Junyan, Guan, Wei, Wu, Rilige, Li, Yan. 2021. High Expression of CLEC11A Predicts Favorable Prognosis in Acute Myeloid Leukemia. In Frontiers in oncology, 11, 608932. doi:10.3389/fonc.2021.608932. https://pubmed.ncbi.nlm.nih.gov/33747924/

8. Fang, Weidan, Wan, Dewen, Yu, Yi, Zhang, Ling. 2024. CLEC11A expression as a prognostic biomarker in correlation to immune cells of gastric cancer. In Biomolecules & biomedicine, 24, 101-124. doi:10.17305/bb.2023.9384. https://pubmed.ncbi.nlm.nih.gov/37597212/