Platelet-rich plasma loaded with antibiotics as an affiliated treatment for infected bone defect by combining wound healing property and antibacterial activity.

To be faced with an infected bone defect and the need to accelerate bone union while controlling infection is a welcome challenge for orthopedists. Platelet-rich plasma (PRP) has been applied in tissue defects given their composition of growth factors however the weak antibacterial effects have limited the use of PRP in the clinical setting. Therefore, the aim of this study was to explore the feasibility of using PRP in a local antibiotic delivery system (PADS) with the characteristics of promoting wound healing of bone infection. PADS was prepared with the addition of antibiotics or no antibiotics as control after PRP was prepared by a two-step centrifugation procedure. Antibacterial tests showed zones of inhibition produced by antibiotics were not significantly different with antibiotics combined with PRP. HPLC analysis demonstrated that about 60% of the total vancomycin (VAN) and ceftazidime (CAZ) dose were released within 10 min, then the release rate gradually decreased. However, 90% clindamycin was released within 10 min. Interestingly, above 10 times the minimum inhibitory concentration was presented after 72 h. Additionally, ELISA and morphology studies of PADS indicated that loaded antibiotics could reduce the PRP-released growth factor concentration and disturb the structure of platelet-fibrin beams and fibrin network in a dose-dependent manner. Fortunately, the lower dose of antibiotics maintained their anti-microbial effect, meanwhile growth factors released from PADS, the structure of platelet-fibrin beams, fibrin network remained unaffected. In addition, a patient experiencing infected bone defect receiving this PADS treatment achieved union within the 15-month follow-up. Therefore, this novel PADS approach might represent a potential therapy for patients who have sustained infected bone defects.

Application of platelet-rich plasma in traumatic bone infections.

Introduction: Traumatic bone infection represents a clinical challenge for orthopedic surgeons. Traditional treatments include surgical debridement and antibiotic, but prolonged use of antibiotic may lead to colonization of resistant bacteria and other adverse reactions.Areas covered: Platelet-rich plasma (PRP), a biological product extracted from the peripheral blood of patients, has been widely used in the field of tissue repair in recent years. Because if its structural and antibacterial properties, PRP is an innovative option for the prevention and treatment of infections. This review assesses the recent scientific literature on PRP, specifically its in the treatment of infections. To this end, a literature review was conducted using the PubMed and Web of Science databases with the following keywords 'platelet-rich plasma (PRP)'; 'PRP AND traumatic bone infections'; 'PRP AND bone defect'; 'PRP AND antibiotics'; and 'PRP AND wound healing'.Expert opinion: This review focuses on the mechanism of action, preparation methods, clinical applications and other aspects related to PRP to provide a reference for its use in the treatment of traumatic bone infections, thereby enhancing the therapeutic effectiveness and improving the prognosis of patients.

New perspectives on traumatic bone infections.

In this paper, we review the results of previous studies and summarize the effects of various factors on the regulation of bone metabolism in traumatic bone infections. Infection-related bone destruction incorporates pathogens and iatrogenic factors in the process of bone resorption dominated by the skeletal and immune systems. The development of bone immunology has established a bridge of communication between the skeletal system and the immune system. Exploring the effects of pathogens, skeletal systems, immune systems, and antibacterials on bone repair in infectious conditions can help improve the treatment of these diseases.

Dendritic cells-derived interferon-λ1 ameliorated inflammatory bone destruction through inhibiting osteoclastogenesis.

Bone infection contributing to inflammatory osteolysis is common in orthopedic surgery. The dynamic balance between bone formation and bone resorption is destroyed due to excessive osteoclast fusion and differentiation, which results in severe bone matrix loss. Many therapeutic approaches that restrain osteoclast formation and function act as efficient ways to prevent inflammatory bone erosion. We have demonstrated for the first time that dendritic cells-derived interferon-λ1 (IFN-λ1) inhibited inflammatory bone destruction in vivo and explored its underlying mechanisms on osteoclast formation in vitro. We found that IFN-λ1 was highly expressed in infectious bone tissue compared with that of non-infectious bone tissue. Additionally, dendritic cells marker genes such as CD80, CD86, and CD1a were higher expressed in infectious bone tissue than that of non-infectious bone tissue. Dendritic cells that were pretreated with LPS showed high expression of IFN-λ1. Moreover, conditioned medium of LPS-pretreated dendritic cells significantly inhibited osteoclast differentiation, as determined by TRAP staining assay. This suppressive effect was reversed by adding an IFN-λ1 monoclonal antibody. It was also investigated whether exogenous IFN-λ1 restrained osteoclastogenesis, bone resorption, F-actin ring formation, osteoclast-specific gene expression, release of pro-inflammatory cytokines, and translocation of p65 and NFATc1 by preventing the NF-κB signaling pathway and NLRP3 inflammasome formation, as well as by inducing the JAK-STAT signaling pathways in vitro. In vivo study indicated that IFN-λ1 prevents lipopolysaccharide (LPS)-induced inflammatory bone destruction by inhibiting excessive osteoclast fusion and bone resorption activity. In conclusion, our findings confirmed that dendritic cells-derived IFN-λ1 could attenuate osteoclast formation and bone resorptive activity in vitro and in vivo. These novel findings pave the way for the use of exogenous IFN-λ1 as a potential therapeutic treatment for excessive osteoclast-related diseases, such as inflammatory osteolysis, by regulating osteoclastogenesis to maintain the dynamic balance between bone formation and bone resorption.

Metacarpal tuberculosis with Nocardia infection: A case report.

INTRODUCTION: Isolated metacarpal tuberculosis is rare in orthopedic surgery. In the case of poor efficacy of traditional treatment methods, such as debridement surgery and anti-tuberculosis treatment, it is necessary to consider whether there is a special type of infection. We describe a case of metacarpal tuberculosis with Nocardia infection in a patient. PATIENT CONCERNS: A 65-year-old male patient who suffered from pain and dysfunction lasted for 6 years. DIAGNOSES: Confirmation of the diagnosis was finally achieved by isolation of M tuberculosis and Nocardia actinomycetes from bone specimens. INTERVENTIONS: The patient underwent debridement surgery, Masquelet technique was used during the operation, and oral antibiotics were combined after surgery. OUTCOMES: Bone graft surgery was performed 6 weeks after the first surgery. We followed up on bone healing at 1 and 3 months postoperatively. CONCLUSION: Tissue-specific necrosis usually occurs in particular types of infections such as tuberculosis, which limits the spread of antibiotics. Masquelet technique seems to bring new options to solve this problem. The performance of Nocardia infection is similar to that of tuberculosis infection, so it is difficult to identify clinically. Therefore, for cases where tuberculosis is suspected, and anti-tuberculosis treatment is ineffective, the possibility of Nocardia infection needs to be considered.

Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF-κB-NFATc1 signal pathway.

Skeletal homeostasis is closely effectuated by the regulation of bone formation and bone resorption. Osteoclasts are multinuclear giant cells responsible for bone resorption. Overactivated osteoclasts and excessive bone resorption result in various lytic bone diseases, such as osteoporosis, osteoarthritis, periprosthetic infection, and inflammatory aseptic loosening of orthopedic implants. In consideration of the severe side effects caused by the currently available drugs, exploitation of novel drugs has gradually attracted attention. Because of its anti-inflammatory, antioxidant, and antitumor capacities, diallyl disulfide (DADS), a major oil-soluble organosulfur ingredient compound derived from garlic, has been widely researched. However, the effects of DADS on osteoclasts and lytic bone diseases are still unknown. In this study, we investigated the effects of DADS on receptor activator of NF-κB ligand (RANKL)- and LPS-mediated osteoclastogenesis, LPS-stimulated proinflammatory cytokines related to osteoclasts, and LPS-induced inflammatory osteolysis. The results showed that DADS significantly inhibited RANKL-mediated osteoclast formation, fusion, and bone resorption in a dose-dependent manner via inhibiting the NF-κB and signal transducer and activator of transcription 3 signaling and restraining the interaction of NF-κB p65 with nuclear factor of activated T cells cytoplasmic 1. Furthermore, DADS also markedly suppressed LPS-induced osteoclastogenesis and reduced the production of proinflammatory cytokines with LPS stimulation to indirectly mediate osteoclast formation. Consistent with the in vitro results, DADS prevented the LPS-induced severe bone loss by blocking the osteoclastogenesis. All of the results indicate that DADS may be a potential and exploitable drug used for preventing and impeding osteolytic lesions.-Yang, J., Tang, R., Yi, J., Chen, Y., Li, X., Yu, T., Fei, J. Diallyl disulfide alleviates inflammatory osteolysis by suppressing osteoclastogenesis via NF-κB-NFATc1 signal pathway.

Streptolysin O derived from Streptococcus pyogenes inhibits RANKL­induced osteoclastogenesis through the NF­κB signaling pathway.

Streptococcus pyogenes (GAS) is a clinically significant bacterial strain that causes bacterial arthritis, osteomyelitis and implant infections. Infection complications can lead to serious bone destruction. Osteoclasts, the only type of cell with bone resorption function, participate in this process. Streptolysin O (SLO) is produced by almost all clinical Streptococcus pyogenes isolates. However, the role of SLO in bone infection caused by GAS had not been previously examined. The current study was performed to define the effects of SLO on receptor activator of NF­κB ligand­stimulated osteoclast differentiation in vitro. Results demonstrated that SLO decreased the phosphorylation of p65 and NF­κB inhibitor α, suppressed c­FOS and nuclear factor of activated T­cells cytoplasmic 1, and downregulated the expression of osteoclast marker genes. SLO also induced apoptosis of mature osteoclasts. The results suggested that SLO blocked osteoclast activation during GAS infection. These findings may prove useful in the development of novel strategies for treating GAS­associated bone infectious diseases.

Interleukin-37 inhibits osteoclastogenesis and alleviates inflammatory bone destruction.

Excessive osteoclast formation is one of the important pathological features of inflammatory bone destruction. Interleukin-37 (IL-37) is an anti-inflammatory agent that is present throughout the body, but it displays low physiological retention. In our study, high levels of the IL-37 protein were detected in clinical specimens from patients with bone infections. However, the impact of IL-37 on osteoclast formation remains unclear. Next, IL-37 alleviated the inflammatory bone destruction in the mouse in vivo. We used receptor activator of nuclear factor-κB ligand and lipopolysaccharide to trigger osteoclastogenesis under physiological and pathological conditions to observe the role of IL-37 in this process and explore the potential mechanism of this phenomenon. In both induction models, IL-37 exerted inhibitory effects on osteoclast differentiation and bone resorption. Furthermore, IL-37 decreased the phosphorylation of inhibitor of κBα and p65 and the expression of nuclear factor of activated T cells c1, while the dimerization inhibitor of myeloid differentiation factor 88 reversed the effects. These data provide evidence that IL-37 modulates osteoclastogenesis and a theoretical basis for the clinical application of IL-37 as a treatment for bone loss-related diseases.

Inhibitory effect of vanillin on RANKL-induced osteoclast formation and function through activating mitochondrial-dependent apoptosis signaling pathway.

Bone matrix homeostasis associated diseases such as osteoporosis and erosive arthritis were caused by the imbalance of osteoclast-mediated bone-resorption and osteoblast-mediated bone-formation. Suppressing the fusion and differentiation of osteoclast from osteoclast precursors are an essential way to maintain the dynamic balance of resorption and formation. Recently, some natural products were discovered to inhibit osteoclast formation and function for potential treatment of osteoporosis. Vanillin was previously reported to have anti-tumor and anti-oxidant activities; however, its effect on bone health has not been elucidated. In this study, we found that the inhibitory effect of vanillin on RANKL-induced multinucleated osteoclast formation and bone resorption (concentration of 0.25 mM-2.5 mM). Morphologically, the number of mature osteoclasts was decreased after treating with vanillin in a dose-dependent manner, which was evaluated by TRAP staining and FAK staining. Vanillin could significantly inhibit bone resorption and promote the early apoptosis rate during RANKL-induced osteoclastogenesis. Furthermore, vanillin could activate the mitochondrial-dependent apoptosis via inducing the expression of cytochrome c, cleaved caspease-3, BAX and Apaf-1 both on mRNA and protein level. Otherwise, the expression of Bcl-2 was inhibited. Thereby, these data provide the clue that vanillin could be a candidate to treat bone matrix metabolic diseases.