Astaxanthin attenuates irradiation-induced osteoporosis in mice by inhibiting oxidative stress, osteocyte senescence, and SASP.

Radiation therapy (RT) is a crucial part of many treatment plans for cancer patients. However, major undesired side effects are associated with this treatment, including impaired bone remodeling and bone loss. Irradiation induces bone loss due to promoted osteoclastic bone resorption and reduced osteoblastic bone formation. Astaxanthin (AST) is a natural antioxidant with anti-oxidative and anti-aging properties. However, it is unclear whether AST is also protective against osteoporosis induced by ionizing radiation (IR). Here, we evaluate the efficacy of AST in mitigating IR-induced bone loss in a mouse model where both hindlimbs received radiation. Reduced BMD, bone biomechanical strength, bone formation, elevated oxidative stress, and osteoclast activity with microarchitectural deterioration of trabecular and cortical bones were observed in IR mice. Supplementation with AST corrected these osteoporotic phenotypes, caused by IR, by inhibiting oxidative stress, DNA damage, osteocyte senescence, and senescence-associated secretory phenotype (SASP), subsequently promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. The results from our study provide experimental evidence for the clinical use of AST to prevent IR-induced osteoporosis in cancer patients.

Treatment with soluble bone morphogenetic protein type 1A receptor fusion protein alleviates irradiation-induced bone loss in mice through increased bone formation and reduced bone resorption.

An increased fracture risk is often observed in cancer patients undergoing radiotherapy (RT), particularly at sites within the field of radiation. Therefore, the development of appropriate therapeutic options to prevent RT-induced bone loss is urgently needed. A soluble form of the BMP receptor type 1A fusion protein (mBMPR1A-mFc) serves as an antagonist to endogenous BMPR1A. Previous studies have shown that mBMPR1A-mFc treatment increases bone mass in both ovary-intact and ovariectomized via promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. The present study was designed to investigate whether mBMPR1A-mFc administration prevents radiation-induced bone deterioration in mice. We constructed an animal model of radiation-induced osteoporosis by exposure to a 2-Gy dose of X-rays. Micro-CT, histomorphometric, bone-turnover, and mechanical analyses showed that mBMPR1A-mFc administration prevented trabecular microarchitecture deterioration after RT because of a marked increase in bone formation and a decrease in bone resorption. Mechanistic studies indicated that mBMPR1A-mFc administration promoted osteoblastogenesis by activating Wnt/Lrp5/ß-catenin signaling while decreasing osteoclastogenesis by inhibiting the RANKL/RANK/OPG pathway. Our novel findings provide solid evidence for the application of mBMPR1A-mFc as a therapeutic treatment for radiation-induced osteoporosis.

lncRNA UCA1 Predicts a Poor Prognosis and Regulates Cell Proliferation and Migration by Repressing p21 and SPRY1 Expression in GC.

Dysregulated expression of long non-coding RNAs (lncRNAs) has been reported in many types of cancers, indicating that it has important regulatory roles in human cancer biology. Recently, lncRNA urothelial cancer-associated 1 (UCA1) was shown to be dysregulated in many cancer types, but the detailed mechanisms remain largely unknown. In our study, we found that upregulated UCA1 is associated with poor prognosis in gastric cancer patients. Further experiments revealed that UCA1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. Moreover, RNA sequencing (RNA-seq) analysis revealed that UCA1 knockdown preferentially affected genes that are linked to cell proliferation, cell cycle, and cell migration. Mechanistically, UCA1 promotes cell proliferation progression through repressing p21 and Sprouty RTK signaling antagonist 1 (SPRY1) expression by binding to EZH2. We found that UCA1 could mediate the trimethylation of H3K27 in promoters of p21 and SPRY1. To our knowledge, this is the first report showing the global gene profile of downstream targets of UCA1 in the progression of gastric cancer. Collectively, our data reveal the important roles of UCA1 in gastric cancer (GC) oncogenesis.

Pyrroloquinoline Quinone Prevents Estrogen Deficiency-Induced Osteoporosis by Inhibiting Oxidative Stress and Osteocyte Senescence.

Accumulating studies have shown that oxidative stress increases with aging, which is related to the pathophysiology of postmenopausal osteoporosis. Pyrroloquinoline quinone (PQQ) is a natural anti-oxidant with anti-oxidative and anti-aging effects. However, it is unclear whether PQQ has a protective role against estrogen deficiency-induced osteoporosis. Here, we evaluated the efficacy of PQQ on bone mineral density, bone microarchitecture, bone turnover and biomechanical strength in ovariectomy (OVX)-induced osteoporosis mouse model. Although dietary PQQ supplement did not affect serum E2 levels and uterine weight in OVX mice, it could prevent OVX-induced bone loss and improve bone strength by inhibiting oxidative stress, osteocyte senescence and senescence-associated secretory phenotype (SASP), subsequently promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption, which was comparable to treatment with exogenous estrogen. The results from our study provide experimental evidence for the clinical use of PQQ to prevent estrogen deficiency-induced osteoporosis.

Nano-sized titanium alloy particles inhibit the proliferation and promote the apoptosis of bone marrow mesenchymal stem cells in vitro.

Aseptic loosening of artificial joints is the leading cause of failure for patients who receive total joint arthroplasty. Prior reports indicate that bone marrow mesenchymal stem cells (BSMC) are critical in the stabilization of implanted artificial joints, and that deregulated interaction between BMSCs and artificial joint derived particles is a risk factor for aseptic loosening with an unknown mechanism. In the present study, the pathomechanisms whereby titanium and its alloy derived particles facilitate aseptic loosing were investigated in vitro. It was demonstrated that nano­sized titanium alloy particles significantly inhibited the proliferation of BMSCs in a time and concentration dependent manner. Furthermore, it was demonstrated that the particles promoted the apoptosis of BMSCs in the same manner. Bax and Caspase­3 expression of BMSCs were elevated when cultured with the particles. As BMSCs exhibit a critical role in the stabilization of artificial joints, the results of the present study may provide a novel direction for the management of aseptic loosening in clinics.