Targeting type H vessels in bone-related diseases.

Blood vessels are essential for bone development and metabolism. Type H vessels in bone, named after their high expression of CD31 and Endomucin (Emcn), have recently been reported to locate mainly in the metaphysis, exhibit different molecular properties and couple osteogenesis and angiogenesis. A strong correlation between type H vessels and bone metabolism is now well-recognized. The crosstalk between type H vessels and osteoprogenitor cells is also involved in bone metabolism-related diseases such as osteoporosis, osteoarthritis, fracture healing and bone defects. Targeting the type H vessel formation may become a new approach for managing a variety of bone diseases. This review highlighted the roles of type H vessels in bone-related diseases and summarized the research attempts to develop targeted intervention, which will help us gain a better understanding of their potential value in clinical application.

Quercitrin attenuates the progression of osteoarthritis via inhibiting NF-κB signaling pathways and enhance glucose transport capacity.

Osteoarthritis (OA) is a common musculoskeletal disorder that impairs function and reduces the quality of life. Extracellular matrix (ECM) degradation and inflammatory mechanisms are crucial to the progression of OA. In this study, we aimed to investigate the anti-inflammatory activity, anti-ECM degradation property, and glucose transport capacity of quercitrin (QCT) on IL-1ß-treated rat primary chondrocytes. Rat primary chondrocytes were treated with IL-1ß to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of QCT at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 5 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model through anterior cruciate ligament transection (ACLT). The animals were then periodically injected with QCT into the knee articular cavity. Our in vivo and in vitro study showed that QCT could inhibit IL-1ß-activated inflammation and ECM degradation in chondrocyte. Furthermore, QCT could inhibit the NF-κB signal pathway and enhance glucose transport capacity in the IL-1ß-stimulated chondrocytes. In vivo study proved that QCT attenuates OA progression in rats. Overall, QCT inhibited the activation of NF-κB and enhanced glucose transport capacity to alleviate the progression of OA.

Self-Assemble Silk Fibroin Microcapsules for Cartilage Regeneration through Gene Delivery and Immune Regulation.

Effective treatments for cartilage defects are currently lacking. Gene delivery using proper delivery systems has shown great potential in cartilage regeneration. However, the inflammatory microenvironment generated by the defected cartilage severely affects the system's delivery efficiency. Therefore, this study reports a silk fibroin microcapsule (SFM) structure based on layer-by-layer self-assembly, in which interleukin-4 (IL-4) is modified on silk by click chemistry and loaded with lysyl oxidase plasmid DNA (LOX pDNA). The silk microcapsules display good biocompatibility and the release rate of genes can be adjusted by controlling the number of self-assembled layers. Moreover, the functionalized SFMs mixed with methacrylated gelatin (GelMA) exhibit good injectability. The IL-4 on the outer layer of the SFM can regulate macrophages to polarize toward the M2 type, thereby promoting cartilage matrix repair and inhibiting inflammation. The LOX pDNA loaded inside can be effectively delivered into cells to promote extracellular matrix generation, significantly promoting cartilage regeneration. The results of this study provide a promising biomaterial for cartilage repair, and this novel silk-based microcapsule delivery system can also provide strategies for the treatment of other diseases.

Quercetin alleviates nanoparticle-induced osteolysis via deactivating pyroptosis.

As one of the most successful stories in modern medicine, total joint arthroplasty (TJA) is performed several million times worldwide every year. However, more than 20% of patients will suffer from aseptic loosening (AL) following periprosthetic osteolysis (PPO) in the next few years. Unfortunately, the only effective treatment for PPO, i.e., revision surgery, can cause great surgical trauma. It has been reported that the accumulation of reactive oxidative species (ROS) generated by exposure to wear particles could activate NLRP3 inflammasome in macrophages and accelerate the progress of osteolysis. Given that the conservative treatment is not effective and can be accompanied by apparent side effects, we, therefore, investigated the therapeutic effect of the natural compound quercetin (Que) on wear particle-induced osteolysis. Our results showed that Que could activate nuclear factor erythroid 2-related factor 2 (Nrf2) to remove ROS and deactivate inflammasome activation. Besides, the imbalance between osteoclastogenesis and osteogenesis induced by inflammatory cytokines was also rescued by Que. Collectively, our work demonstrates that Que may be a qualified candidate for the conservative treatment of wear particle-induced osteolysis.

Gardenoside ameliorates inflammation and inhibits ECM degradation in IL-1ß-treated rat chondrocytes via suppressing NF-κB signaling pathways.

Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment beside late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Gardenoside is a naturally compound extracted from Gardenia jasminoides Ellis, which has a variety of anti-inflammatory effects. However, few studies have been conducted to determine the role of gardenoside in OA. This study aimed to explore whether gardenoside has effect in OA treatment. Rat primary chondrocytes were treated with IL-1ß to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of gardenoside at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Via in vitro experiments, our study found that gardenoside lowers the gene expression of COX-2, iNOS, IL-6, and reduced the ROS production of chondrocytes induced by IL-1ß. Moreover, it effectively alleviates ECM degradation caused by IL-1ß and promotes the ECM synthesis in chondrocytes by upregulating collagen-II and the ACAN expression, downregulating the expression of MMP-3, MMP-13, and ADAMTS-5 expression. Further, our study showed that gardenoside inhibits NF-κB signaling pathway activated by IL-1ß in chondrocytes. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with gardenoside into the knee articular cavity. In vivo study suggested that gardenoside attenuates OA progression in rats. As a whole, in vitro and in vivo results highlight gardenoside is a promising OA treatment agent.

Madecassic Acid Ameliorates the Progression of Osteoarthritis: An in vitro and in vivo Study.

Purpose: Osteoarthritis (OA) places a significant burden on society and finance, and there is presently no effective treatment besides late replacement surgery and symptomatic relief. The therapy of OA requires additional research. Madecassic acid (MA) is the first native triterpenoid compound extracted from Centella asiatica, which has a variety of anti-inflammatory effects. However, the role of MA in OA therapy has not been reported. This study aimed to explore whether MA could suppress the inflammatory response, preserve and restore chondrocyte functions, and ameliorate the progression of OA in vitro and in vivo. Methods: Rat primary chondrocytes were treated with IL-1ß to simulate inflammatory environmental conditions and OA in vitro. We examined the effects of MA at concentrations ranging from 0 to 200 µM on the viability of rat chondrocytes and selected 10 µM for further study. Using qRT-PCR, immunofluorescent, immunocytochemistry, and Western blotting techniques, we identified the potential molecular mechanisms and signaling pathways that are responsible for these effects. We established an OA rat model by anterior cruciate ligament transection (ACLT). The animals were then periodically injected with MA into the knee articular cavity. Results: We found that MA could down-regulate the IL-1ß-induced up-regulation of COX-2, iNOS and IL-6 and restore the cytoskeletal integrity of chondrocytes treated with IL-1ß. Moreover, MA protects chondrocytes from IL-1ß-induced ECM degradation by upregulating ECM synthesis related protein expression, including collagen-II and ACAN, and further down-regulating ECM catabolic related protein expression, including MMP-3 and MMP-13. Furthermore, we found that NF-κB/IκBα and PI3K/AKT signaling pathways were involved in the regulatory effects of MA on the inflammation inhibition and promotion of ECM anabolism on IL-1ß-induced chondrocytes. Conclusion: These findings suggest that MA appears to be a potentially small molecular drug for rat OA.

A case report of old injury of lateral collateral ligament of knee joint combined with injury of common peroneal nerve.

Since common peroneal nerve is easy be injured because of superficial position of caput fibulae, less surrounding soft tissue and poor mobility, injury of common peroneal nerve is a problem worth discussing in the field of trauma orthopedics. Common peroneal nerve injury often causes foot prolapse, inability in dorsiflexion and eversion, sensory disturbance of anterolateral side of the lower leg and dorsum of foot. In this article, a case of old injury of lateral collateral ligament of knee joint combined with an avulsion fracture of fibular head resulting in injury of common peroneal nerve was reported and repaired by surgery with good effects.

Nucleus pulposus cell senescence is regulated by substrate stiffness and is alleviated by LOX possibly through the integrin ß1-p38 MAPK signaling pathway.

Intervertebral disc degeneration (IVDD) is a main contributor to induce low back pain, and the pathogenic mechanism of IVDD remains unclear. The nucleus pulposus (NP) is a component of the intervertebral disc (IVD) that provides protection from mechanical stimuli. The matrix stiffness of NP tissue increases during the process of disc degeneration. Although several studies have found that pathological mechanical stimuli induce NP cell senescence, which is relevant for NP degeneration, however, the effect of matrix stiffness on NP cell senescence is not clear. Therefore, in the present study, we used polyvinyl alcohol (PVA) hydrogel with controllable stiffness to mimic the matrix stiffness of normal (4 kPa) and severely degenerated (20 kPa) NP tissue. Rat NP cells were isolated and cultured on substrates with different stiffness, and the cell proliferation, SA-ß-gal activity, cell cycle, telomerase activity and the phenotype markers of NP cells were analyzed. Moreover, cytoskeleton staining and NP cellular Young's modulus on different substrates were also measured. To further investigate how substrate stiffness affects NP cell senescence, lysyl oxidase (LOX) was used to restore the extracellular matrix (ECM) synthesis of NP cells. The expression levels of integrin ß1 and p38 MAPK were then measured. Our results showed that the 20 kPa substrate significantly induced NP cell senescence compared to the 4 kPa substrate. NP cells cultured on the 20 kPa substrate failed to maintain the expression of their phenotype markers. Furthermore, the 20 kPa substrate induced an increase of Young's modulus of NP cells, which possibly through up regulating the expressions of integrin ß1 and p38 MAPK. These results indicated that the integrin ß1-p38 MAPK signaling pathway may participated in substrate stiffness induced senescence of NP cells. LOX significantly increased ECM synthesis and inhibited substrate stiffness induced NP cell senescence, which indicated that matrix mechanics may be essential for maintaining the function of NP cell. Our results may provide a new perspective on the mechanism of IVDD by pathological matrix mechanics.

Ankle arthroscopy-assisted closed reduction in Bosworth fracture dislocation.

The Bosworth fracture dislocation is a rare type of ankle fracture and is usually unrecognized on initial radiographs, therefore early open reduction is recommended. This study reports a 51-year-old female with uncommon imaging and clinical features. Preoperative X-ray, computed tomography, and magnetic resonance imaging of the ankle showed posterior detached dislocation of the intact distal fibula, the loose osteochondral fragments located in the tibiotalar joint, and the rupture of the deltoid ligament. Due to the initial infected wound on the severely swollen ankle, delayed arthroscopy-assisted closed reduction and internal fixation, removal of loose bodies, and repair of the deltoid ligament were performed, 19 days after injury. Postoperative imaging, including the X-ray, computed tomography, and magnetic resonance imaging, demonstrated the anatomic reduction of the ankle joint. After 6 months of follow-up, the patient gained a pain-free motion of the ankle with a range of passive 10° dorsiflexion and 40° plantar flexion, and resumed her normal gait and activity. This report indicates that the detached posterior dislocation of the intact distal fibula is a rare variant of the Bosworth fracture dislocation, and suggests that arthroscopy-assisted closed reduction and removal of loose osteochondral fragments in joint space are useful technique for this special type of the Bosworth lesions.

High failure rate of proximal femoral locking plates in fixation of trochanteric fractures.

BACKGROUND: The aim of this study was to report our previous results of treatments for trochanteric fractures with proximal femoral locking plates (PFLP) and to analyze the underlying mechanisms and possible risk factors associated with the high failure rate of this technique. METHODS: From January 2010 to October 2014, 273 consecutive patients with trochanteric femoral fractures were identified, and 95 patients (with 97 fractures) ultimately met the inclusion criteria. Clinical records regarding demographic features and intraoperative data including total incision length, operation time, blood loss, and failures detected in radiographs were documented and assessed. The collected data were analyzed with SPSS 19.0 software. RESULTS: The stable group (AO/OTA 31 A1 and A2.1) had less blood loss than the unstable group (AO/OTA 31 A2.2, A2.3, and A3). The ultimate failure rate was 36% in 97 fractures. The obvious complications in this study included nonunion in 7 (7.2%) fractures, implant breakage in 4 (4.1%) fractures, varus deformity in 34 (35%) fractures, and loosening of the proximal femoral screw in 21 (21.6%) fractures. Six patients received reoperations. The total failure rate in the stable group was 17% and was 50% in the unstable group. In patients greater than 60 years old in the unstable group, the failure rate was 60.5%. CONCLUSIONS: High failure rates of PFLP were observed in patients with trochanteric fracture, especially in patients who were greater than 60 years old with unstable fracture types. PFLP was not an appropriate treatment for trochanteric fractures.

Modified Technique of Separate Vertical Wiring for the Fixation of Patellar Inferior Pole Fracture.

To evaluate the biomechanical and clinical results of modified separate vertical wiring technique (SVW) for inferior pole patellar fracture repair we conducted a finite element biomechanical study using 2 fixation methods and evaluated a clinical series of eleven patients. The modified SVW technique was an effective, safe and simple method that can provide stable fixation for early exercise with excellent functional results in fixing inferior pole patella fractures.