The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1β were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1β-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.

No abstract

With the evergrowing threat posed by multidrug resistance of bacteria, the development of effective antibacterial agents remains a global challenge. Infection with multidrug-resistant bacteria in hospitals significantly impairs the healing of wounds caused by deep-burn injuries or diabetic foot ulceration, leading to a high mortality rate among these patients. A multivalent glycosheet for the double light-driven therapy against multidrugresistant Pseudomonas aeruginosa (P. aeruginosa) infection on wounds is developed here. Galactose-and fucose-based ligands are self-assembled to form a glyco-layer on the surface of thin-layer molybdenum disulfide, producing the glycosheets capable of selectively localizing P. aeruginosa through multivalent carbohydrate-lectin interactions. The glycosheets loaded with antibiotics have proven applicable for: 1) near-infrared-light driven, in situ thermal release of antibiotics, increasing bacterial membrane permeability, and 2) white light-driven reactive-oxygen-species production to more thoroughly kill the bacteria. The targetability, together with the light sensibility, of the glycosheets enables a highly effective and optically controlled therapeutic regime for the healing of wounds infected by multidrug-resistant as well as clinically isolated P. aeruginosa.

Osteoarthritis (OA) and osteoporosis (OP) are two skeletal disorders associated with joint structures. Occasionally, OA and OP occur in the same patient. However, the effect of OP changes on OA progression in patients with osteoporotic OA (OP‐OA) has not been reported, especially the potential association between subchondral bone and articular cartilage. Thus we investigated the alterations in the microstructure, biomechanical properties, and remodeling of subchondral bone as well as their association with cartilage damage in the hip joint of patients with OP‐OA. Thirty‐nine femoral head specimens were obtained from patients who underwent total hip arthroplasty (OA group, n = 19; OP‐OA group, n = 20), and healthy specimens from cadaver donors were used (control group, n = 10). The microstructure and biomechanical properties of subchondral bone were evaluated by micro–computed tomography and micro–finite‐element analysis. Histology, histomorphometric measurements, and immunohistochemistry were used to assess subchondral bone remodeling and cartilage damage. Linear regression analysis was performed to elucidate the relationship between subchondral bone and articular cartilage. In the subchondral bone of the OP‐OA group, compared with that of the OA group, aberrant bone remodeling leads to an inferior microstructure and worsening biomechanical properties, potentially affecting transmission of loading stress from the cartilage to the subchondral bone, and then resulting in accelerated OA progression in patients with OP‐OA. The results indicate that changes in subchondral bone could affect OA development and the improvement in subchondral bone with bone‐metabolism agents may help mitigate OA progression when OP and OA coexist in the same patients. © 2019 American Society for Bone and Mineral Research.

Background: Knee osteoarthritis (OA) is a common disabling disease involving the entire joint tissue, and its onset and progression are affected by many factors. However, the current number of studies investigating the relationship between subchondral trabecular bone (STB), knee alignment, and OA severity is limited. We aimed to investigate the variation in tibial plateau STB microarchitecture in end-stage knee OA patients and their association with knee alignment (hip-knee-ankle, HKA, angle) and OA severity. Methods: Seventy-one knee OA patients scheduled for total knee arthroplasty (TKA) underwent preoperative radiography to measure the HKA angle and Kellgren-Lawrence grade. Tibial plateaus collected from TKA were scanned using micro-computed tomography to analyze the STB microarchitecture. Histological sections were used to assess cartilage degeneration (OARSI score). Correlations between the HKA angle, OA severity (OARSI score, Kellgren-Lawrence grade), and STB microarchitecture were evaluated. Differences in STB microstructural parameters between varus and valgus alignment groups based on the HKA angle were examined. Results: The HKA angle was significantly correlated with all STB microarchitecture parameters (p < 0.01). The HKA angle was more correlated with the medial-to-lateral ratios of the microarchitecture parameters than with the medial or lateral tibia plateaus. The HKA angle and all STB microarchitecture parameters are significantly correlated with both the OARSI score and Kellgren-Lawrence grade (p < 0.01). Conclusions: The STB microarchitecture is associated with the HKA angle and OA severity. With the increase of the knee alignment deviation and OA severity, the STB of the affected side tibial plateau increased in bone volume, trabecular number, and trabecular thickness and decreased in trabecular separation.

The treatment of Chiari malformation type 1 (CM-I) with posterior fossa decompression without (PFD) or with duraplasty (PFDD) is controversial. Our aim is to compare the clinical outcome between the two methods for the treatment of CM-I. In this paper, the authors report a systematic review and meta-analysis of operation time, clinical improvement, and complications of PFD compared with PFDD for the treatment of CM-I. Randomized or non-randomized controlled trials of PFD and PFDD were considered for inclusion. Twelve published reports of eligible studies involving 841participants meet the inclusion criteria. There is significant difference in the operative time [mean difference = -74.63, 95 % CI (-83.02, -66.25), p < 0.05] in favor of PFD compared with PFDD. There is significant difference in overall complication rates [mean difference = 0.34, 95 % CI (0.19, 0.60), p < 0.05] and rates of CSF leak [mean difference = 0.24, 95 % CI (0.07, 0.78), p < 0.05] in favor of PFD groups. However, there is significant difference in the clinical improvement rate in favor of the PFDD group [mean difference = 0.85, 95 % CI (0.73, 0.99), p < 0.05]. Although PFDD is related with longer operation time and higher CSF leak rate, it can still be considered as a preferable treatment option for most CM-I patients for its higher improvement rate. More evidence from advanced multi-center studies are needed to provide illumination for the surgical decision making of CM-I.

We report the construction of a biodegradable macroporous scaffold with a nano-crystal surface microstructure capable of releasing bioactive ions for highly effective osteogenesis and vascularization.

Implant-related infection is a devastating complication in clinical trauma and orthopedics. The aim of this study is to use a bifunctional biomaterial surface in order to investigate the competitive colonization between osteoblasts and bacteria, which is the cause of implant-related infection. A bone-engineering material capable of simultaneously facilitating osteoblast adhesion and inhibiting the growth of Staphylococcus aureus (S. aureus) was prepared. Then, three different co-cultured systems were developed in order to investigate the competitive colonization between the two cohorts on the surface. The results suggested that while the pre-culturing of either cohort compromised the subsequent adhesion of the other according to the ‘race for the surface’ theory, the synergistic effect of preferential cell adhesion and antibacterial activity of the bifunctional surface led to the predominant colonization and survival of osteoblasts, effectively inhibiting the bacterial adhesion and biofilm formation of S. aureus in the co-culture systems with both cohorts. This research offers new insight into the investigation of competitive surface-colonization between osteoblasts and bacteria for implant-related infection.