Association between LEPR polymorphism and susceptibility of osteoporosis in Chinese Mulao people.

To explore the association between the single nucleotide polymorphism (SNP) of leptin receptor (LEPR) gene and the susceptibility to osteoporosis (OP) among Chinese Mulao people. A total of 738 people were involved. Bone mineral density (BMD) was examined by calcaneus ultrasound attenuation measurement. Six SNPs of LEPR were detected. The genotypes, allele frequencies, linkage disequilibrium, and haplotype were analyzed. BMD decreased with age and males had higher BMD than women. The proportion of normal bone mass decreased with age, and morbidity of OP increased. Three out of six SNPs showed a difference between OP and normal group. Individuals with AA genotype of rs1137100 in OP group outnumber the normal group, AA increased the risk of OP. In rs2767485, CT increased the risk of OP, C allele may be susceptible to OP. TT genotype of rs465555 was susceptible genotype of OP, T locus may be associated with OP. Strong linkage disequilibrium was detected among rs1137100, rs1137101, and rs4655555. Four haplotypes were constructed, among which, AACGCT and GGTGTA increased the risk of OP by 3.9 and 4.2 times, respectively, whereas, GGCGTA reduced 74% of OP susceptibility. The rs1137100, rs2767485, and rs465555 of LEPR were associated with OP in Chinese Mulao people.

S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells.

Multiple myeloma (MM) is a lethal hematological malignancy characterized by abundant myeloid cells in the microenvironment that fuel tumor progression. But the mechanism by which myeloid cells support myeloma cells has not been fully explored. We aimed to examine their effect on bone marrow cells of MM patients by scRNA-seq transcriptome analysis and reveal a high-resolution gene profile of myeloma cells and myeloma-associated myeloid cells. Based on correlation analysis of integrated scRNA-seq and bulk RNA-seq datasets from patients, we confirmed that myeloid-derived S100A9 was involved in TNFSF13B-dependent myeloma cell proliferation and survival. In the animal experiments, S100A9 was found to be critical for MM cell proliferation and survival via TNFSF13B production by myeloid cells, neutrophils, and macrophages. In-vitro analysis of patient primary myeloma cells further demonstrated that enhanced TNFSF13B signaling triggered the canonical NF-κB pathway to boost tumor cell proliferation. All these results suggest that myeloid-derived S100A9 is required for TNFSF13B/TNFRSF13B-dependent cell-fate specification, which provides fresh insights into MM progression.