Lycopene Improves Bone Quality in SAMP6 Mice by Inhibiting Oxidative Stress, Cellular Senescence, and the SASP.

SCOPE: Cellular senescence (CS) is closely related to tissue ageing including bone ageing. CS and the senescence-associated secretory phenotype (SASP) have emerged as critical pathogenesis elements of senile osteoporosis. This study aims to investigate the effect of lycopene on senile osteoporosis. METHODS AND RESULTS: The senescence-accelerated mouse prone 6 (SAMP6) strain of mice is used as the senile osteoporosis model. Daily ingestion of lycopene for 8 weeks preserves the bone mass, density, strength, and microarchitecture in the SAMP6 mice. Moreover, these alterations are associated with a decrease in oxidative stress in the senile osteoporosis model. In addition, there is a reduction in osteoblast and osteocyte senescence and the SASP in the bone tissues of the SAMP6 mice. Lycopene improves bone health likely due to its antioxidant properties that may be linked with the regulation of CS and SASP in the SAMP6 mice. CONCLUSION: These results suggest that lycopene may be beneficial for the management of senile osteoporosis by inhibiting oxidative stress, CS, and the SASP.

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.

Downregulation of IRAK3 by miR-33b-3p relieves chondrocyte inflammation and apoptosis in an in vitro osteoarthritis model.

Interleukin-1 receptor-associated kinase-3 (IRAK3) has a distinctive role in regulating inflammation. However, the functional role of IRAK3 and regulatory mechanism underlying the pathogenesis of osteoarthritis (OA) remain unclear. Here, we first found that IRAK3 was upregulated, while miR-33b-3p was downregulated in the cartilage of OA patients and IL-1ß-induced CHON-001 cells. IRAK3 was confirmed as the direct target of miR-33b-3p and negatively regulated by miR-33b-3p. There was an inverse correlation between IRAK3 mRNA expression and miR-33b-3p expression in OA cartilage tissues. The in vitro functional experiments showed that miR-33b-3p overexpression caused a remarkable increase in viability, a significant decrease in inflammatory mediators (IL-1ß and TNF-α), and apoptosis in IL-1ß-induced CHON-001 cells. Importantly, IRAK3 knockdown imitated, while overexpression reversed the effects of miR-33b-3p on IL-1ß-induced inflammation and apoptosis in CHON-001 cells. Collectively, miR-33b-3p significantly alleviated IL-1ß-induced inflammation and apoptosis by downregulating IRAK3, which may serve as a promising target for OA.

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.

A soluble bone morphogenetic protein type 1A receptor fusion protein treatment prevents glucocorticoid-Induced bone loss in mice.

Glucocorticoid-induced osteoporosis (GIOP) is a frequent complication of systemic glucocorticoid (GC) therapy, is the most common form of secondary osteoporosis, and is associated with skeletal fragility and increased fracture risk. A soluble form of BMP receptor type 1A fusion protein (mBMPR1A-mFc) acts as an antagonist to endogenous BMPR1A and could increase bone mass in both ovariectomized and ovary-intact mice, but its effects in GIOP mice remained unclear. The aim of this study was to evaluate the effects of mBMPR1A-mFc on the skeleton in experimental models of GIOP. mBMPR1A-mFc treatment could increase the bone mineral density (BMD), trabecular bone volume, thickness, and number, and cortical thickness, and reduce the structure model index and trabecular separation in GIOP mice. mBMPR1A-mFc treatment could also prevent bone loss and enhance biomechanical strength in GIOP mice by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption. Mechanistic studies revealed that mBMPR1A-mFc treatment increased murine osteoblastogenesis by activating the Wnt/ß-catenin signaling pathway while decreasing osteoclastogenesis by inhibiting the RANK/RANKL/osteoprotegerin (OPG) signaling pathway. These findings demonstrate that mBMPR1A-mFc treatment in GIOP mice improves bone mass, microarchitecture, and strength by enhancing osteoblastic bone formation and inhibiting osteoclastic bone resorption in GIOP mice and offers a promising novel alternative for the treatment of GIOP.