Abstract
Wear particle-induced aseptic prosthetic loosening is a major complication associated with total joint arthroplasty (TJA). A growing body of evidence suggests that receptor activator of nuclear factor κ-B ligand (RANKL)-stimulated osteoclastogenesis and bone resorption are responsible for peri-implant loosening. Thus, agents which attenuate excessive osteoclast differentiation and function have been considered to offer therapeutic potential for prolonging the life of TJA implants. Jatrorrhizine hydrochloride (JH), a major protoberberine alkaloid isolated from the traditional Chinese herb Coptis chinensis, has been reported to have antimicrobial, antitumor, and antihypercholesterolemic and neuroprotective activities. However, its effects on osteoclast biology remain unknown. Here, we found that JH inhibited RANKL-induced osteoclast formation and bone resorption in vitro and exerted protection against titanium (Ti) particle-induced osteolysis in vivo. Biochemical analysis demonstrated that JH suppressed RANKL-induced activation of MAPKs (p38 and ERK) which down-regulated the production of NFATc1 and NFATc1-regulated osteoclastic marker genes, such as TRAP, CTR and CTSK. Collectively, our findings suggest that JH may be a promising anti-osteoclastogenesis agent for treating periprosthetic osteolysis or other osteoclast-related osteolytic diseases.
Highlights
Total joint arthroplasty (TJA) is an effective procedure for treating end-stage joint diseases such as rheumatoid arthritis and osteoarthritis [1]
Our results showed that Bone marrow-derived macrophages (BMMs) viability or proliferation was not affected by Jatrorrhizine hydrochloride (JH) treatment, even at concentration as high as 160 μM. (Figure 3F)
Our study clearly demonstrated that JH exerted inhibitory actions on osteoclast formation and function in vitro and in vivo, indicating that this compound may be a therapeutic candidate for treating osteolysis
Summary
Total joint arthroplasty (TJA) is an effective procedure for treating end-stage joint diseases such as rheumatoid arthritis and osteoarthritis [1]. Several strategies have been developed to overcome this problem, including improving the implant designs, perfecting surgical techniques, and searching for better biomaterials. During the last two decades, many agents have been demonstrated to target osteoclast function and suppress wear debris-stimulated bone resorption, such as bisphosphonates [8,9], erythromycin [10] and denosumab [11]. Their long-term use could cause severe side effects, including digestive system disorders, osteonecrosis, and even some types of malignancy [12,13,14,15].
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