Design and performance of pH-responsive cyano-Raman label SERS probes based on single urchin Au nanoparticles.

A cyano-Raman label pH-responsive SERS probe was constructed by immobilizing 6-MPN molecules onto the surface of a single urchin Au nanoparticle (AuNP). The effects of different conditions on the synthetic materials were investigated and the optical properties of the single nanoparticles were evaluated. The peak-strength ratio of SERS probes at 1589 cm-1 and 2240 cm-1 exhibited a linear relationship in the pH range 4-7. The properties and stability of the probe were also verified by the acid-base cycle and ion interference tests.

Effect of gestational weight gain on postpartum pelvic floor function in twin primiparas: a single-center retrospective study in China.

BACKGROUND: The effect of gestational weight gain (GWG) as a controllable factor during pregnancy pelvic floor function has rarely been investigated, and studies on twin primiparas are even less frequent. The objective of the present study was to explore the effect of GWG on postpartum pelvic floor function in twin primiparas. METHODS: We retrospectively analyzed the clinical data of 184 twin primiparas in the pelvic floor rehabilitation system of the First Affiliated Hospital of Chongqing Medical University from January 2020 to October 2021. Based on the GWG criteria recommended by the Institute of Medicine, the study subjects were classified into two groups: adequate GWG and excessive GWG. Univariate and multivariate logistic regression models were applied to explore the relationship between GWG and pelvic floor function. RESULTS: Among the 184 twin primiparas, 20 (10.87%) had excessive GWG. The rates of abnormal vaginal dynamic pressure (95% vs. 74.39%), injured type I muscle fibers (80% vs. 45.73%), anterior vaginal wall prolapse (90% vs. 68.90%), and stress urinary incontinence (50% vs. 20.12%) of twin primiparas with excessive GWG were significantly higher than those with adequate GWG. There was no significant difference between the total score of the Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20) or the scores of the Pelvic Organ Prolapse Distress Inventory 6 (POPDI-6), the Colorectal-Anal Distress Inventory 8 (CRADI-8), and the Urinary Distress Inventory 6 (UDI-6) in the two groups (P > 0.05). After adjusting for potential confounding factors, the results showed that excessive GWG was positively associated with abnormal vaginal dynamic pressure (OR = 8.038, 95% CI: 1.001-64.514), injured type I muscle fibers (OR = 8.654, 95% CI: 2.462-30.416), anterior vaginal wall prolapse (OR = 4.705, 95% CI: 1.004-22.054), and stress urinary incontinence (OR = 4.424, 95% CI: 1.578-12.403). CONCLUSION: Excessive GWG in twin primiparas was positively correlated with the prevalence of pelvic floor dysfunction but did not exacerbate pelvic floor symptoms in twin primiparas. Controlling GWG within a reasonable range is recommended for reducing the risk of PFDs in pregnant women with twins.

Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression.

Abnormal subchondral bone remodeling featured by overactivated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is unclear. We used lymphocyte cytosolic protein 1 (Lcp1) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and Lcp1-/- mice showed decreased bone remodeling in subchondral bone and retarded cartilage degeneration. For mechanisms, the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor 1 alpha subunit (HIF-1α) in chondrocytes and led to cartilage degeneration. Lcp1 knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Last, we showed that Oroxylin A, an Lcp1-encoded protein l-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.

Smart Hydrogels for Bone Reconstruction via Modulating the Microenvironment.

Rapid and effective repair of injured or diseased bone defects remains a major challenge due to shortages of implants. Smart hydrogels that respond to internal and external stimuli to achieve therapeutic actions in a spatially and temporally controlled manner have recently attracted much attention for bone therapy and regeneration. These hydrogels can be modified by introducing responsive moieties or embedding nanoparticles to increase their capacity for bone repair. Under specific stimuli, smart hydrogels can achieve variable, programmable, and controllable changes on demand to modulate the microenvironment for promoting bone healing. In this review, we highlight the advantages of smart hydrogels and summarize their materials, gelation methods, and properties. Then, we overview the recent advances in developing hydrogels that respond to biochemical signals, electromagnetic energy, and physical stimuli, including single, dual, and multiple types of stimuli, to enable physiological and pathological bone repair by modulating the microenvironment. Then, we discuss the current challenges and future perspectives regarding the clinical translation of smart hydrogels.

ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis.

Stem cell-based therapy has drawn attention as an alternative option for promoting prosthetic osteointegration in osteoporosis by virtue of its unique characteristics. However, estrogen deficiency is the main mechanism of postmenopausal osteoporosis. Estrogen, as an effective antioxidant, deficienncy also results in the accumulation of reactive oxygen species (ROS) in the body, affecting the osteogenic differentiation of stem cells and the bone formation i osteoporosis. In this study, we prepared a ROS-scavenging hydrogel by crosslinking of epigallocatechin-3-gallate (EGCG), 3-acrylamido phenylboronic acid (APBA) and acrylamide. The engineered hydrogel can scavenge ROS efficiently, enabling it to be a cell carrier of bone marrow-derived mesenchymal stem cells (BMSCs) to protect delivered cells from ROS-mediated death and osteogenesis inhibition, favorably enhancing the tissue repair potential of stem cells. Further in vivo investigations seriously demonstrated that this ROS-scavenging hydrogel encapsulated with BMSCs can prominently promote osteointegration of 3D printed microporous titanium alloy prosthesis in osteoporosis, including scavenging accumulated ROS, inducing macrophages to polarize toward M2 phenotype, suppressing inflammatory cytokines expression, and improving osteogenesis related markers (e.g., ALP, Runx-2, COL-1, BSP, OCN, and OPN). This work provides a novel strategy for conquering the challenge of transplanted stem cells cannot fully function in the impaired microenvironment, and enhancing prosthetic osteointegration in osteoporosis.

Postoperative Pneumonia in Geriatric Patients With a Hip Fracture: Incidence, Risk Factors and a Predictive Nomogram.

Objectives: To evaluate the incidence and risk factors of postoperative pneumonia (POP) in geriatric patients with a hip fracture after surgery, to design a predictive nomogram, and to validate the accuracy of the nomogram. Design: Retrospective study. Setting: A tertiary hospital affiliated to a medical university. Patients/Participants: We retrospectively studied 1285 surgical-treated geriatric patients with a hip fracture from April 2010 to April 2018. Intervention: Surgical treatment was performed on the patients of this study. The procedure methods were classified as: total hip arthroplasty, hemiarthroplasty, percutaneous fixation, intramedullary nail fixation, and plate/screw fixation. Main Outcome Measurement: The primary interest of end point of this study is the development of POP during the postoperative period. The postoperative period in this study was defined as the time from 24 hours after surgery to discharge. The diagnostic criteria for pneumonia were set according to the guidelines built by the Infectious Diseases Society of America and the American Thoracic Society (Guidelines for the Management of Adults with Hospital-Acquired, Ventilator-Associated, and Healthcare-Associated Pneumonia, 2005). Potential variables for developing POP were identified using logistic regression analyses initially and were further selected via the method of LASSO. Then the independent risk factors were identified by multivariable regression analyses. A predictive nomogram was built based on the multiple regression model, and the calibration abilities of the nomogram was measured by Harrel C-index, calibration plot and Hosmer-Lemeshow test, respectively. Decision curve analysis was carried out to assess the net benefit due to threshold probability and an on-line questionnaire survey was conducted among the clinicians to assess the applicability of the nomogram coherently. Results: Of the 1285 patients, 70 (5.4%) developed POP. COPD, number of comorbidities, ASA classification >2, preoperative dependent functional status and cognitive impairment were identified as independent risk factors of POP. The nomogram built based on the results showed good accordance between the predicted probabilities and the observed frequency. The decision curve analysis confirmed the clinical utility of the nomogram when the threshold probabilities were between 5% and 65% due to the net benefit, while the results of on-line questionnaire among 200 clinicians showed that 91.5% of the participants had a mental threshold of intervention between 5-50%. Conclusion: (1). COPD, number of comorbidities, ASA classification >2, preoperative dependent functional status and cognitive impairment are independent risk factors for POP. (2). The nomogram built in this study has a good accordance between the predictive risk and the observational incidence. The results of decision curve and questionnaire among clinicians show well applicability of the nomogram.

[Morphological analysis of coronal femoral intertrochanteric fracture and its effect on reduction and internal fixation].

OBJECTIVE: To investigate the morphology of coronal femoral intertrochanteric fracture and its effect on reduction and internal fixation. METHODS: The clinical and imaging data of 46 patients with femoral intertrochanteric fracture who met the selection criteria between August 2017 and October 2018 were reviewed. There were 15 males and 31 females; the age ranged from 62 to 91 years, with an average of 72.8 years. The causes of injury included walking falls in 35 cases, falling out of bed in 4 cases, and traffic accidents in 7 cases. The AO/Orthopaedic Trauma Association classification was type 31-A1 in 11 cases and type 31-A2 in 35 cases. All patients underwent closed reduction and internal fixation with intramedullary nails. During the operation, fracture reduction and fixation were performed according to the preoperative evaluation results. According to the patients' preoperative X-ray film and CT three-dimensional reconstruction images, the direction of the coronal fracture line of the femoral intertrochanter and the morphological characteristics of the fracture block were observed; and the coronal fracture discrimination analysis was carried out for the fractures of different AO/OTA types. The percentages of coronal femoral intertrochanteric fractures diagnosed by preoperative X-ray film and CT three-dimensional reconstruction were calculated and statistically analyzed. The fracture reduction, the position of internal fixation [measurement of tip-apex distance (TAD)]. and the reliability of internal fixation were observed after operation. RESULTS: X-ray film was not easy to identify coronary fracture, and the coronal fracture line and the shape of the fracture piece weree clearly visible in CT three-dimensional reconstruction images. The morphological characteristics of the coronary fracture block: in AO/OTA 31-A1 type, the fracture line extended obliquely backward from the anterior tip of the large rotor, above the small rotor with or without small rotor fracture; in AO/OTA 31-A2 type, fracture line extended obliquely backward from the anterior tip of the large rotor to below the small rotor. Thirteen cases (28.3%) of coronal fractures were found on preoperative X-ray films, and 35 cases (76.1%) were found by CT three-dimensional reconstruction, showing significant difference ( χ 2=21.083, P=0.000). In AO/OTA 31-A1 type patients, the proportion of coronal fractures found by X-ray film and CT three-dimensional reconstruction was 18.2% (2/11) and 54.5% (6/11), respectively, and that in AO/OTA 31-A2 type patients was 31.4% (11/35) and 82.9% (29/35), respectively, showing significant differences ( χ 2=3.143, P=0.000; χ 2=20.902, P=0.000). Among the 35 patients with coronal fractures, 6 cases (17.1%) of AO/OTA 31-A1 type, 29 cases (82.9%) of AO/OTA 31-A2 type. The operation time of the patient was 80-112 minutes, with an average of 95 minutes; the intraoperative blood loss was 180-450 mL, with an average of 360 mL. There was no complication such as infection, falling pneumonia, and deep vein thrombosis of the lower extremities. At 3 days after operation, the internal fixators were all in the proper position. The TAD was 0.9-1.8 cm, with an average of 1.4 cm. All patients were followed up 14-18 months, with an average of 16 months. All the fractures healed osseously, and there was no complication such as nonunion and loosening of internal fixation. CONCLUSION: CT three-dimensional reconstruction can better identify coronal femoral intertrochanteric fractures than X-ray films, and accurately recognize and analyze the incidence and morphological characteristics of coronal fractures, which can help formulate more effective surgical strategies to promote patient recovery.

RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss.

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter-driven Cre expression (AdipoqCre ) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre ; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)-induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.

Targeting actin-bundling protein L-plastin as an anabolic therapy for bone loss.

The actin-bundling protein L-plastin (LPL) mediates the resorption activity of osteoclasts, but its therapeutic potential in pathological bone loss remains unexplored. Here, we report that LPL knockout mice show increased bone mass and cortical thickness with more mononuclear tartrate-resistant acid phosphatase-positive cells, osteoblasts, CD31hiEmcnhi endothelial vessels, and fewer multinuclear osteoclasts in the bone marrow and periosteum. LPL deletion impeded preosteoclasts fusion by inhibiting filopodia formation and increased the number of preosteoclasts, which release platelet-derived growth factor-BB to promote CD31hiEmcnhi vessel growth and bone formation. LPL expression is regulated by the phosphatidylinositol 3-kinase/AKT/specific protein 1 axis in response to receptor activator of nuclear factor-κB ligand. Furthermore, we identified an LPL inhibitor, oroxylin A, that could maintain bone mass in ovariectomy-induced osteoporosis and accelerate bone fracture healing in mice. In conclusion, we showed that LPL regulates osteoclasts fusion, and targeting LPL serves as a novel anabolic therapy for pathological bone loss.

One-Step Preparation of an AgNP-nHA@RGO Three-Dimensional Porous Scaffold and Its Application in Infected Bone Defect Treatment.

BACKGROUND: Bactericidal capacity, durable inhibition of biofilm formation, and a three-dimensional (3D) porous structure are the emphases of infected bone defect (IBD) treatment via local scaffold implantation strategy. PURPOSE: In this study, silver nanoparticle (AgNP)-loaded nano-hydroxyapatite (nHA)@ reduced graphene oxide (RGO) 3D scaffolds (AHRG scaffolds) were designed to alleviate bone infection, inhibit biofilm formation, and promote bone repair through the synergistic effects of AgNPs, RGO, and nHA. MATERIALS AND METHODS: AHRGs were prepared using a one-step preparation method, to create a 3D porous scaffold to facilitate a uniform distribution of AgNPs and nHA. Methicillin-resistant Staphylococcus aureus (MRSA) was used as a model-resistant bacterium, and the effects of different silver loadings on the antimicrobial activity and cytocompatibility of materials were evaluated. Finally, a rabbit IBD model was used to evaluate the therapeutic effect of the AHRG scaffold in vivo. RESULTS: The results showed successful synthesis of the AHRG scaffold. The ideal 3D porous structure was verified using scanning electron microscopy and transmission electron microscopy, and X-ray photoelectron spectroscopy and selected area electron diffraction measurements revealed uniform distributions of AgNP and nHA. In vitro antibacterial and cytocompatibility indicated that the 4% AHRG scaffolds possessed the most favorable balance of bactericidal properties and cytocompatibility. In vivo evaluation of the IBD model showed promising treatment efficacy of AHRG scaffolds. CONCLUSION: The as-fabricated AHRG scaffolds effectively eliminated infection and inhibited biofilm formation. IBD repair was facilitated by the bactericidal properties and 3D porous structure of the AHRG scaffold, suggesting its potential in the treatment of IBDs.

Neobavaisoflavone inhibits osteoclastogenesis through blocking RANKL signalling-mediated TRAF6 and c-Src recruitment and NF-κB, MAPK and Akt pathways.

Psoralea corylifolia (P corylifolia) has been popularly applied in traditional Chinese medicine decoction for treating osteoporosis and promoting fracture healing since centuries ago. However, the bioactive natural components remain unknown. In this study, applying comprehensive two-dimensional cell membrane chromatographic/C18 column/time-of-flight mass spectrometry (2D CMC/C18 column/TOFMS) system, neobavaisoflavone (NBIF), for the first time, was identified for the bioaffinity with RAW 264.7 cells membranes from the extracts of P corylifolia. Here, we revealed that NBIF inhibited RANKL-mediated osteoclastogenesis in bone marrow monocytes (BMMCs) and RAW264.7 cells dose dependently at the early stage. Moreover, NBIF inhibited osteoclasts function demonstrated by actin ring formation assay and pit-formation assay. With regard to the underlying molecular mechanism, co-immunoprecipitation showed that both the interactions of RANK with TRAF6 and with c-Src were disrupted. In addition, NBIF inhibited the phosphorylation of P50, P65, IκB in NF-κB pathway, ERK, JNK, P38 in MAPKs pathway, AKT in Akt pathway, accompanied with a blockade of calcium oscillation and inactivation of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In vivo, NBIF inhibited osteoclastogenesis, promoted osteogenesis and ameliorated bone loss in ovariectomized mice. In summary, P corylifolia-derived NBIF inhibited RANKL-mediated osteoclastogenesis by suppressing the recruitment of TRAF6 and c-Src to RANK, inactivating NF-κB, MAPKs, and Akt signalling pathways and inhibiting calcium oscillation and NFATc1 translocation. NBIF might serve as a promising candidate for the treatment of osteoclast-associated osteopenic diseases.

Macro-Microporous Surface with Sulfonic Acid Groups and Micro-Nano Structures of PEEK/Nano Magnesium Silicate Composite Exhibiting Antibacterial Activity and Inducing Cell Responses.

PURPOSE: To improve the surface bio-properties of polyetheretherketone (PEEK)/nano magnesium silicate (n-MS) composite (PC). MATERIALS AND METHODS: The surface of PC was firstly treated by particle impact (PCP) and subsequently modified by concentrated sulfuric acid (PCPS). RESULTS: PCPS surface exhibited not only macropores with sizes of about 150 µm (fabricated by particle impact) but also micropores with sizes of about 2 µm (created by sulfonation of PEEK) on the macroporous walls, and sulfonic acid (-SO3H) groups were introduced on PCPS surface. In addition, many n-MS nanoparticles were exposed on the microporous walls, which formed micro-nano structures. Moreover, the surface roughness and hydrophilicity of PCPS were obviously enhanced as compared with PC and PCP. Moreover, the apatite mineralization of PCPS in simulated body fluid (SBF) was obviously improved as compared with PC. Furthermore, compared with PC and PCP, PCPS exhibited antibacterial performances due to the presence of -SO3H groups. In addition, the responses (eg, adhesion and proliferation as well as differentiation) of bone marrow mesenchymal stem cell of rat to PCPS were significantly promoted as compared with PC and PCP. CONCLUSION: PCPS with macro-microporous surface containing -SO3H groups and micro-nano structures exhibited antibacterial activity and induced cell responses, which might possess large potential for bone substitute and repair.

Guaiacol suppresses osteoclastogenesis by blocking interactions of RANK with TRAF6 and C-Src and inhibiting NF-κB, MAPK and AKT pathways.

Angelica sinensis (AS; Dang Gui), a traditional Chinese herb, has for centuries been used for the treatment of bone diseases, including osteoporosis and osteonecrosis. However, the effective ingredient and underlying mechanisms remain elusive. Here, we identified guaiacol as the active component of AS by two-dimensional cell membrane chromatography/C18 column/time-of-flight mass spectrometry (2D CMC/C18 column/TOFMS). Guaiacol suppressed osteoclastogenesis and osteoclast function in bone marrow monocytes (BMMCs) and RAW264.7 cells in vitro in a dose-dependent manner. Co-immunoprecipitation indicated that guaiacol blocked RANK-TRAF6 association and RANK-C-Src association. Moreover, guaiacol prevented phosphorylation of p65, p50, IκB (NF-κB pathway), ERK, JNK, c-fos, p38 (MAPK pathway) and Akt (AKT pathway), and reduced the expression levels of Cathepsin K, CTR, MMP-9 and TRAP. Guaiacol also suppressed the expression of nuclear factor of activated T-cells cytoplasmic 1(NFATc1) and the RANKL-induced Ca2+ oscillation. In vivo, it ameliorated ovariectomy-induced bone loss by suppressing excessive osteoclastogenesis. Taken together, our findings suggest that guaiacol inhibits RANKL-induced osteoclastogenesis by blocking the interactions of RANK with TRAF6 and C-Src, and by suppressing the NF-κB, MAPK and AKT signalling pathways. Therefore, this compound shows therapeutic potential for osteoclastogenesis-related bone diseases, including postmenopausal osteoporosis.

Myostatin Promotes Osteoclastogenesis by Regulating Ccdc50 Gene Expression and RANKL-Induced NF-κB and MAPK Pathways.

Myostatin is a crucial cytokine that is widely present in skeletal muscle and that negatively regulates the growth and development of muscle cells. Recent research has shown that myostatin might play an essential role in bone metabolism. In RAW264.7 cells and bone marrow monocytes (BMMCs), myostatin activates the expression of the II type receptor ActR II B. Here, we report that myostatin significantly promoted RANKL/M-CSF-induced osteoclastogenesis and activated NF-κB and MAPK pathways in vitro via the Ccdc50 gene. Overexpression of myostatin promoted osteoclastogenesis and osteoclastogenesis-related markers including c-Src, MMP9, CTR, CK, and NFATc1. Specifically, myostatin increased the phosphorylation of Smad2, which led to the activation of NF-κB and MAPK pathways to activate osteoclastogenesis. Ccdc50 was identified as a gene whose expression was highly decreased in osteoclastogenesis upon myostatin treatment, and it could inhibit the function of myostatin in osteoclastogenesis by blocking NF-κB and MAPKs pathways. Our study indicates that myostatin is a promising candidate target for inhibiting RANKL-mediated osteoclastogenesis and might participate in therapy for osteoporosis, and that the Ccdc50 gene plays a significant role in the regulatory process.

l-tetrahydropalmatine suppresses osteoclastogenesis in vivo and in vitro via blocking RANK-TRAF6 interactions and inhibiting NF-κB and MAPK pathways.

Bone homeostasis is delicately orchestrated by osteoblasts and osteoclasts. Various pathological bone loss situations result from the overactivated osteoclastogenesis. Receptor activator of nuclear factor κB ligand (RANKL)-activated NF-κB and MAPK pathways is vital for osteoclastogenesis. Here, we for the first time explored the effects of l-tetrahydropalmatine (l-THP), an active alkaloid derived from corydalis, on the formation and function of osteoclasts in vitro and in vivo. In RAW264.7 cells and bone marrow monocytes cells (BMMCs), l-THP inhibited osteoclastic differentiation at the early stage, down-regulated transcription level of osteoclastogenesis-related genes and impaired osteoclasts functions. Mechanically, Western blot showed that l-THP inhibited the phosphorylation of P50, P65, IκB, ERK, JNK and P38, and the electrophoretic mobility shift assay (EMSA) revealed that DNA binding activity of NF-κB was suppressed, ultimately inhibiting the expression of nuclear factor of activated T cells (NFATc1). Besides, Co-immunoprecipitation indicated that l-THP blocked the interactions of RANK and TNF receptor associated factor 6 (TRAF6) at an upstream site. In vivo, l-THP significantly inhibited ovariectomy-induced bone loss and osteoclastogenesis in mice. Collectively, our study demonstrated that l-THP suppressed osteoclastogenesis by blocking RANK-TRAF6 interactions and inhibiting NF-κB and MAPK pathways. l-THP is a promising agent for treating osteoclastogenesis-related diseases such as post-menopausal osteoporosis.

Aligned Carbon Nanotubes Reduce Hypertrophic Scar via Regulating Cell Behavior.

Hypertrophic scars, characterized by excessive cell proliferation, disordered cell growth, and aberrant deposition of collagens, could cause significant clinical problems. Herein, aligned carbon nanotubes (ACNTs) were synthesized via chemical vapor deposition, and bulk ACNTs were pulled out from the arrays. The capacity of the ACNTs to reduce hypertrophic scar formation was evaluated both in vitro and in vivo. The results demonstrated that the ACNTs suppressed the overproliferation of fibroblast cells, directed their growth, and inhibited collagen expression in vitro without cell cytotoxicity. Moreover, in vivo evaluation in a rabbit ear model indicated relieved scar hypertrophy after the ACNTs treatment. The gene expression microarray was further used to understand the mechanism, which showed that ACNTs could inhibit the TGFß pathway to alter the components in the extracellular matrix, cell proliferation, cell cytoskeleton, and cell motility. These findings may provide a potent strategy of using carbon nanotubes in the bioengineering field.

Matrine derivate MASM uncovers a novel function for ribosomal protein S5 in osteoclastogenesis and postmenopausal osteoporosis.

Postmenopausal osteoporosis (POMP) is a public health problem characterized by decreased bone density and increased fracture risk. Over-activated osteoclastogenesis plays a vital role in POMP. Here we developed a novel bioactive compound MASM (M19) based on sophocarpine. Although it showed no significant effects on osteogenesis and adipogenesis for bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, it could significantly inhibit RANKL/M-CSF induced osteoclastogenesis through suppressing NF-κB, MAPKs and PI3K/Akt pathways in vitro and ameliorate bone loss in ovariectomized mice in vivo. Ribosomal protein s5 (RPS5) has been identified as a target of M19 and regulates PI3K/Akt, NF-κB and MAPKs pathways in osteoclastogenesis. Overexpressions of RPS5 synergistically inhibited osteoclastogenesis with M19 while silencing RPS5 compromised M19 inhibitory effects on osteoclastogenesis in vitro. Among the three pathways, Akt plays a major role in M19 effects. The Akt activator SC79 partially reversed the inhibitory effects on osteoclastogenesis by M19 and RPS5-knocking-down. It indicates that RPS5 serves as a potential candidate target for inhibiting osteoclastogenesis and osteoporosis therapy and M19 is a promising agent for POMP treatment.

Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.

Osteoporosis is a metabolic bone disease characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content. The imbalance between osteogenesis by osteoblasts and osteoclastogenesis by osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis. Estrogen withdrawal leads to increased levels of proinflammatory cytokines. Overactivated osteoclasts by inflammation play a vital role in the imbalance. Matrine is an alkaloid found in plants from the Sophora genus with various pharmacological effects, including anti-inflammatory activity. Here we demonstrate that matrine significantly prevented ovariectomy-induced bone loss and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b, TNF-α, and IL-6. In vitro matrine significantly inhibited osteoclast differentiation induced by receptor activator for NF-κB ligand (RANKL) and M-CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption through pit formation assays. For molecular mechanisms, matrine abrogated RANKL-induced activation of NF-κB, AKT, and MAPK pathways and suppressed osteoclastogenesis-related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K. Our study demonstrates that matrine inhibits osteoclastogenesis through modulation of multiple pathways and that matrine is a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.-Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L., Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.

Promotion of in vivo degradability, vascularization and osteogenesis of calcium sulfate-based bone cements containing nanoporous lithium doping magnesium silicate.

Nanoporous lithium doping magnesium silicate (nl-MS) was introduced into calcium sulfate hemihydrate to prepare calcium sulfate composite (nl-MSC) bone cements. The introduction of nl-MS improved the in vitro degradability of nl-MSC cements, which could neutralize acidic degradable products of calcium sulfate and prevented the pH from dropping. The cements were implanted into the bone defects of femur bone of rabbits, and the results of histological and immunohistochemical analysis revealed that massive new bone tissue formed in the defects while the cements were degradable, indicating that the osteogenesis and degradability of the nl-MSC cements were much better than the control calcium sulfate dihydrate (CSD) cements. Furthermore, the positive expression of vascular endothelial growth factor and collagen type I for nl-MSC cements was higher than CSD, indicating that addition of nl-MS into the cements enhanced vascularization and osteogenic differentiation. The results suggested that the nl-MSC cements with good biocompatibility and degradability could promote vascularization and osteogenesis, and had great potential to treat bone defects.