Joint replacement is a common surgical procedure for the terminal stages of degenerative joint diseases including rheumatoid arthritis and osteoarthritis. 1 Despite advances in surgical procedures and prosthetic material, peri-prosthetic osteolysis and the resulting aseptic loosening remains a major complication leading to implant failure. 2 Titanium (Ti)-based biomaterials are by far the most commonly used prosthetic implants due to their superiority in load-bearing applications and excellent mechanical strength and resilience. 3 However, it has now been suggested that wear particles derived from the metal biomaterial provoke an inflammatory response that subsequently induces osteoclast-mediated bone destruction around the bone-implant interface. 4 The underlying molecular mechanism that bridges the initial inflammatory response to subsequent bone destruction is complex but involves the production and release of chemokines and cytokines that predominantly promote osteoclast recruitment and activity causing localized bone loss. 5
Balanced bone resorption and bone formation are vital for bone homeostasis. Excessive osteoclastic bone resorption in this process can cause a variety of bone disorders including osteoporosis, aseptic prosthetic loosening and tumor associated bone destruction. Bulleyaconitine A (BLA) is a natural compound that has been widely used for pain treatment but its role in osteolysis has not yet been investigated. In this study, we verified for the first time that BLA inhibited osteoclast formation, the mRNA expression of osteoclast-related genes and osteoclastic bone resorption by inhibiting NF-κB signal pathway and downstream NFATc1 expression. Meanwhile, BLA had a stimulatory effect in osteoblast differentiation and mineralization. Furthermore, BLA showed preventive effect in Ti particle-induced osteolysis model in vivo. Together, all our data demonstrated that BLA suppressed osteoclastogenesis and promoted osteoblastogenesis via suppressing NF-κB signal pathway and could be an alternative therapeutic choice against bone loss.
Acylglycerol kinase (AGK) is a recently discovered mitochondrial lipid kinase, and mutation of its gene is the fundamental cause of Sengers syndrome. AGK is not only involved in the stability of lipid metabolism but also closely related to mitochondrial protein transport, glycolysis, and thrombocytopoiesis. Evidence indicates that AGK is an important factor in the occurrence and development of tumors. Specifically, AGK has been identified as an oncogene that partakes in the regulation of tumor cell growth, invasion, metastasis, and drug resistance. The versatility of AGK and its unique role in different types of cancerous and normal cells greatly piqued our interest. We believe that AGK is a promising target for cancer therapy. Therefore, this review summarizes the main research advances concerning AGK, including the discovery of its physiological/pathogenic mechanisms, and provides a reference for the feasible evaluation of AGK as a therapeutic target for human diseases, particularly tumors.
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