Osteoarthritis (OA) is the main cause of disability in the elderly. Effective intervention in the early and middle stage of osteoarthritis can greatly prevent or slow down the development of the disease, and reduce the probability of joint replacement. However, there is to date no effective intervention for early and middle-stage OA. OA microenvironment mainly destroys the balance of oxidative stress, extracellular matrix synthesis and degradation of chondrocytes under the joint action of biological and mechanical factors. Herein, hollow Prussian blue nanozymes (HPBzymes) were designed via a modified hydrothermal template-free method. The aim of this study was to investigate the effects of HPBzymes on chondrocytes and the progression of OA. The intrinsic bioactivities of HPBzymes were excavated in vitro and in vivo, remodeling microenvironment for significantly protecting chondrocytes and delaying the progression of traumatic OA by inhibiting reactive oxygen species (ROS) and Rac1/nuclear factor kappa-B (NF-κB) signaling in a rat model. HPBzyme significantly diminished interleukin (IL)-1β-stimulated inflammation, extracellular matrix degradation, and apoptosis of human chondrocytes. HPBzyme attenuated the expression of Rac1 and the ROS levels and prevented the release and nuclear translocation of NF-κB. Deeply digging the intrinsic bioactivities of nanozyme with single component to remodel microenvironment is an effective strategy for ROS-associated chronic diseases. This study reveals that excavating the bioactivities of nanomedicine deserves attention for diagnosis and treatment of severe diseases.

The imbalance of bone homeostasis is the root cause of osteoporosis. However current therapeutic approaches mainly focus on either anabolic or catabolic pathways, which often fail to turn the imbalanced bone metabolism around. Herein we reported that a SIRT-1 agonist mediated molecular therapeutic strategy to reverse the imbalance in bone homeostasis by simultaneously regulating osteogenesis and osteoclastogenesis via locally sustained release of SRT2104 from mineral coated acellular matrix microparticles. Immobilization of SRT2104 on mineral coating (MAM/SRT) harnessing their electrostatic interactions resulted in sustained release of SIRT-1 agonist for over 30 days. MAM/SRT not only enhanced osteogenic differentiation and mineralization, but also attenuated the formation and function of excessive osteoclasts via integrating multiple vital upstream signals (β-catenin, FoxOs, Runx2, NFATc1, etc.) in vitro. Osteoporosis animal model also validated that it accelerated osteoporotic bone healing and improved osseointegration of the surrounding bone. Overall, our work proposes a promising strategy to treat osteoporotic bone defects by reversing the imbalance in bone homeostasis using designated small molecule drug delivery systems.

To better clinical outcomes, open reduction and internal fixations (ORIFs) have been commonly performed in the case of closed displaced intra-articular calcaneal fractures (CDICFs). Nonetheless, postoperative wound complications remain a significant problem. Therefore, the aim of our study is to summarise relevant evidence investigating the risk factors for postoperative wound complications of CDICFs following ORIFs. A meta-analysis was conducted on relevant clinical studies to identify the risk factors for wound complications of CDICFs after ORIFs. Electronic databases were searched for all relevant studies up to October 2014. The Newcastle-Ottawa scale was used to evaluate the methodological quality, and study-specific odds ratios (ORs) were pooled using the fixed-effects model or random-effects model. Sensitivity analysis and meta-regression analysis was performed to evaluate the heterogeneity. Ten observational studies involving 1559 patients with 1651 fractures were included in this meta-analysis. The results showed that diabetes (OR, 9.76; p < 0.01), no drainage (OR, 5.86; p < 0.01), fracture severity (OR, 3.31; p < 0.01) and bone graft (OR, 1.74; p < 0.01) were the risk factors for wound complications of CDICFs after ORIFs. A trend of more wound complications in patients with a history of smoking was detected. However, female patients, ORIFs performed within 14 days of injury, smoking, hypertension and drinking did not significantly increase the risk of wound complications (p > 0.05). Based on available relevant evidence, bone graft, diabetes, no drainage and fracture severity were all associated with an increased risk of wound complications after ORIF for CDICFs.

The aim of this study is to evaluate the effects of tourniquet release before wound closure for hemostasis or after wound closure in cemented total knee arthroplasty (TKA). We conducted a meta-analysis and review work on relevant clinical outcomes to evaluate the effects of the timing of tourniquet release in cemented TKA. Electronic databases were searched for relevant randomized controlled trials (RCTs) that compared outcomes of tourniquet release before wound closure for hemostasis with tourniquet release after wound closure. The methodological quality of each included RCT was assessed in terms of the 12-item scale. The meta-analysis was performed with STATA 12.0 software. Eleven RCTs involving 651 patients with 670 TKAs were included in this meta-analysis. Of these, 332 patients (342 knees) were in an early tourniquet release group and 319 patients (328 knees) in the late tourniquet release group. The results showed that there were no significant differences in overt blood loss, hemoglobin drop, and blood transfusions, whereas the tourniquet release after wound closure might increase the risks of overall complications and major complications. Tourniquet release before wound closure for hemostasis might reduce the rate of complications, but it could not limit overall blood loss. The current evidences are not enough to indicate that tourniquet release before wound closure is superior to its release after wound closure in cemented TKA.

Objectives: Insulin‐like growth factor‐binding protein 7 (IGFBP7) is a low‐affinity insulin growth factor (IGF) binder that may play an important role in bone metabolism. We previously reported that IGFBP7 enhanced osteogenic differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) via the Wnt/β‐catenin signalling pathway. In this study, we tried to reveal its function in osteoclast differentiation and osteoporosis.Methods: We used both in vitro and in vivo studies to investigate the effects of IGFBP7 on RANKL‐induced osteoclastogenesis and osteoporosis, together with the underlying molecular mechanisms of these processes.Results: We show that IGFBP7 inhibited receptor activation of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclastogenesis, F‐actin ring formation and bone resorption, which was confirmed by using recombinant IGFBP7 protein, lentivirus and siRNA. The NF‐κB signalling pathway was inhibited during this process. Moreover, in a mouse ovariectomy‐induced osteoporosis model, IGFBP7 treatment attenuated osteoporotic bone loss by inhibiting osteoclast activity.Conclusions: Taken together, these findings show that IGFBP7 suppressed osteoclastogenesis in vitro and in vivo and suggest that IGFBP7 is a negative regulator of osteoclastogenesis and plays a protective role in osteoporosis. These novel insights into IGFBP7 may facilitate the development of potential treatment strategies for oestrogen deficiency‐induced osteoporosis and other osteoclast‐related disorders.

Forkhead box protein A2 (FOXA2) is a core transcription factor that controls cell differentiation and may have an important role in bone metabolism. However, the role of FOXA2 during osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remains largely unknown. In this study, decreased expression of FOXA2 was observed during osteogenic differentiation of rat BMSCs (rBMSCs). FOXA2 knockdown significantly increased osteoblast-specific gene expression, the number of mineral deposits and alkaline phosphatase activity, whereas FOXA2 overexpression inhibited osteogenesis-specific activities. Moreover, extracellular signal-regulated protein kinase (ERK) signalling was upregulated following knockdown of FOXA2. The enhanced osteogenesis due to FOXA2 knockdown was partially rescued by an ERK inhibitor. Using a rat tibial defect model, a rBMSC sheet containing knocked down FOXA2 significantly improved bone healing. Collectively, these findings indicated that FOXA2 had an essential role in osteogenic differentiation of BMSCs, partly by activation of the ERK signalling pathway.