Osteoporosis is a progressive skeletal disorder characterized by the decline of bone mineral density and quality, destruction of bone microstructure, and increase of bone fragility. In menopausal women, estrogen deficiency up-regulates RANKL which further activates the NF-κB pathway and MAPK pathway, leading to osteoclast differentiation and bone loss. At the meantime, estrogen deficiency will up-regulate TNF-α to induce apoptosis of osteoblast and down-regulation of RUNX2 and OSX, resulting in the failure of osteoblast differentiation and inhibition of mineralized nodule production. Given the important roles of RANKL and TNF-α in osteoporosis, therapies that can scavenge RANKL and TNF-α hold great potentials for anti-osteoporosis treatment. In the clinic, OPG and antibodies such as Denosumab have been widely applied for scavenging RANKL and suppressing osteoporosis. However, these RANKL/TNF-α inhibitors often suffer from shortcomings such as short blood circulation time, suboptimal biodistribution, complex manufacturing processes, and resistance of antibodies. In addition, the pathological background of osteoporosis is often related to multiple targets, and thus a single-target therapeutic modality may be suboptimal. Therefore, there is an urgent demand for safer and more effective medications for osteoporosis treatment.
Recently, the research group of Prof. Lichen Yin developed pre-osteoclast (RAW 264.7 cell) membrane-coated PLGA nanodecoys (denoted as RAW-PLGA nanodecoys) as RANKL and TNF-α-scavenging agents for the management of postmenopausal osteoporosis. The RAW-PLGA nanodecoys were anticipated to mimic the source cells, displaying abundant RANK and TNF-αR on the nano-surfaces. Thus, the nanodecoys could bind and scavenge RANKL and TNF-α that would otherwise target monocytes and pre-osteoblasts, respectively, hampering osteoclastogenesis yet promoting osteoblastogenesis to suppress osteoporosis. This is the first report of using cell membrane-coated nanodecoys for osteoporosis treatment, and it is also the first example of RANKL scavenging using membrane proteins. The biomimetic nanodecoys therefore provide an effective strategy for reconstructing the osteoclast/osteoblast balance, and hold great potentials for the clinical management of postmenopausal osteoporosis(Sci. Adv.2021, 7, abl6432).
The first author, Mr. Yang Zhou, is from FUNSOM, Soochow University.
Link to paper:https://www.science.org/doi/10.1126/sciadv.abl6432
Link to Prof. Lichen Yin’s group:https://www.x-mol.com/groups/lichen_yin
Acknowledgment: This study was supported by The National Natural Science Foundation of China (51873142), Collaborative Innovation Center of Suzhou Nano Science & Technology, The 111 project, and Joint International Research Laboratory of Carbon-Based Functional Materials and Devices.
Editor: Danting Xiang