Osteosarcoma is a primary bone malignancy with a high rate of recurrence and poorer prognosis. Therefore, it is of vital importance to explore novel prognostic molecular biomarkers and targets for more effective therapeutic approaches. Previous studies showed that histone demethylase KDM5A can increase the proliferation and metastasis of several cancers. However, the function of KDM5A in the carcinogenesis of osteosarcoma is not clear. In the current study, KDM5A was highly expressed in osteosarcoma than adjacent normal tissue. Knockdown of KDM5A suppressed osteosarcoma cell proliferation and induced apoptosis. Moreover, knockdown of KDM5A could increase the expression level of P27 (cell-cycle inhibitor) and decrease the expression of Cyclin D1. Furthermore, after knockout of KDM5A in osteosarcoma cells by CRISPR/Cas9 system, the tumor size and growth speed were inhibited in tumor-bearing nude mice. RNA-Seq of KDM5A-KO cells indicated that interferon, epithelial–mesenchymal transition (EMT), IL6/JAK/STAT3, and TNF-α/NF-κB pathway were likely involved in the regulation of osteosarcoma cell viability. Taken together, our research established a role of KDM5A in osteosarcoma tumorigenesis and progression.

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Osteoporosis is a metabolic skeletal disorder characterized by increased fragility and fracture risk as s result of reduced bone mineral density and microstructural destruction and caused a heavy burden on families and society. Current medicines, on the other hand, have some limitations, with side effects and doubts regarding long-term efficacy being highlighted. Studies seeking for natural constituents as potential treatment options therefore come into focus. Icariin is a phytochemical derived from a traditional Chinese medicine, Herba epimedium, that has been used to treat orthopedic disorders in ancient China for thousands of years, including osteoporosis, osteoarthritis, and fracture. Icariin belongs to a category of prenylated flavonoids and has been shown to help reduce osteoporosis bone loss while having relatively low side effects. Icariin's anti-osteoporosis properties manifest in a variety of ways, like promoting osteogenesis, suppressing osteoclastogenesis and bone resorption, regulating migration, proliferation, and differentiation of mesenchymal stem cells, enhancing angiogenesis, anti-inflammation, and antioxidation. These procedures entail a slew of critical signaling pathways, such as PPARγ, ERα/AKT/β-catenin, and MAPK. Therefore, icariin can be an applicable alternative to improve osteoporosis although the underlying mechanisms have yet to be fully understood. In this study, we searched using the terms “icariin” and “osteoporosis,” and included 64 articles meeting the inclusion criteria and reviewed the research of icariin in anti-osteoporosis over the last 10 years, and discussed new prospects for future study. Therefore, this review may provide some references for further studies.

Osteosarcomas are prevalent in children and young adults and have a high recurrence rate. Cisplatin, doxorubicin, and methotrexate are common adjuvant chemotherapy drugs for treatment of osteosarcoma, but multidrug resistance is a growing problem. Therefore, understanding the molecular mechanisms of chemotherapy resistance in osteosarcoma cells is crucial for developing new therapeutic approaches and ultimately improving the prognosis of osteosarcoma patients. To identify genes associated with cisplatin resistance in osteosarcoma, we screened a large‐scale mutant library generated by transfecting human osteosarcoma cells with a piggyBac (PB) transposon‐based gene activation vector. Several candidate genes were identified by using Splinkerette‐PCR paired with Next Generation Sequencing. We created a disease‐free survival predictor model, which includes ZNF720 , REEP3 , CNNM2 , and CGREF1 , using TARGET (Therapeutically Applicable Research to Generate Effective Treatments) datasets. Additionally, the results of our enrichment analysis between the Four_genes_high group and Low_group suggested that these four genes may participate in cisplatin resistance in osteosarcoma through cross talk between various signaling pathways, especially the signaling pathway related to bone formation. These data may help guide future studies into chemotherapy for osteosarcoma.