Comparison of percutaneous cannulated screw fixation and calcium sulfate cement grafting versus minimally invasive sinus tarsi approach and plate fixation for displaced intra-articular calcaneal fractures: a prospective randomized controlled trial.

BACKGROUND: The management of displaced intra-articular calcaneal fractures (DIACFs) remains challenging and controversial. A prospective randomized controlled trial was conducted to compare percutaneous reduction, cannulated screw fixation and calcium sulfate cement (PR+CSC) grafting with minimally invasive sinus tarsi approach and plate fixation (MISTA) for treatment of DIACFs. METHODS: Ultimately, 80 patients with a DIACFs were randomly allocated to receive either PR+CSC (N = 42) or MISTA (N = 38). Functional outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores. Radiological results were assessed using plain radiographs and computed tomography (CT) scans, and postoperative wound-related complications were also recorded. RESULTS: The average time from initial injury to operation and the average operation time in the PR+CSC group were both significantly shorter than those in the MISTA group (p < 0.05). There were significantly fewer complications in the PR+CSC group than those in the MISTA group (7.1 % vs 28.9 %, p < 0.001). The calcaneal width immediate postoperatively and at the final follow-up in the MISTA group were obviously improved compared to those in the PR+CSC group (p < 0.001). The variables of sagittal motion and hindfoot motion of the AOFAS scoring system in the PR+CSC group were significantly higher than those in the MISTA group (p < 0.05). The good and excellent results in the two groups were comparable for Sanders Type-II calcaneal fractures, but the good to excellent rate in the MISTA group was significantly higher for Sanders Type-III fractures (p < 0.05). CONCLUSION: The clinical outcomes are comparable between the two minimally invasive techniques in the treatment of Sanders Type-II DIACFs. The PR+CSC grafting is superior to the MISTA in terms of the average time between initial injury and operation, operation time, wound-related complications and subtalar joint activity. However, the MISTA has its own advantages in improving the calcaneal width, providing a more clear visualization and accurate reduction of the articular surface, especially for Sanders Type-III DIACFs. TRIAL REGISTRATION: ChiCTRIOR16008512 . 21 May 2016.

Shorter survival rate in varus-aligned knees after total knee arthroplasty.

PURPOSE: One long-held tenet of total knee arthroplasty (TKA) is that post-operative neutral limb alignment promotes implant durability. Recently, the concept of generic safe zone (0° ± 3°) has been challenged. This meta-analysis aimed to evaluate whether neutral alignment was superior to malalignment in long-term survival of TKAs. METHODS: The MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Chinese Periodical, Google and reference lists of all the included studies were searched. Of the 1512 studies initially identified, ten met the eligibility criteria, including eight case-control studies and two cohort trials. Relative risks of implant failure were compared between post-operative neutrally aligned and malaligned knees. RESULTS: Post-operative malalignment showed higher failure rate of knee implants compared with neutral alignment (95 % CI 1.00-1.88, P = 0.05). Failure rate in knees with varus alignment was significantly higher than with neutral alignment (95 % CI 1.07-2.55, P = 0.02). There was no significant difference in the likelihood of implant failure between knees with valgus and neutral alignment (95 % CI 0.78-2.41, n.s.). No significant difference of failure rate was noted between neutral alignment and malalignment for fixed-bearing prothesis (95 % CI 0.94-1.95, n.s.) or rotating-platform prothesis (95 % CI 0.75-2.73, n.s.). There was no significant difference of failure rate between knees with neutral alignment and malalignment for studies with a mean follow-up of more than 10 years (95 % CI 0.81-2.01, n.s.) or studies using long-leg weight-bearing radiographs (95 % CI 0.79-1.79, n.s.). CONCLUSIONS: Post-operative varus alignment results in shorter survival rate after TKA. Not only neutral limb alignment but also the valgus alignment promotes implant durability. Neutral or valgus alignment rather than varus alignment is essential to achieve long-term survival of TKAs and patient satisfaction. LEVEL OF EVIDENCE: III.

Protective effects of sesamin on liver fibrosis through antioxidative and anti-inflammatory activities in rats.

CONTEXT: Sesamin (Ses) from Sesamun indicum seeds has potent antioxidants and anti-inflammatory effects. OBJECTIVE: This study focused on the antioxidant and anti-inflammatory effects of Ses on Carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats and the potential mechanism underlying the activation of NF-kB pathway. MATERIALS AND METHODS: Hepatic fibrosis was induced by interaperitoneally (i.p.) administered with 20% CCl4 in corn oil (2 mL/kg for 8 weeks) in rats. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were checked. The levels of protein carbonyls and antioxidant enzymes such as superoxide dismutase (SOD) and GSH-Px were determined after Ses administration. H&E and Masson's trichrome staining for histopathological changes of liver tissues were observed. Western blotting was used to detect expression of IL-6, cyclooxygenase-2 (COX-2), and NF-kB activation. Finally, the levels of hydroxyproline in liver tissues were also determined. RESULTS: Ses decreased the release of liver enzymes - ALT, AST, and TBIL, reduced protein carbonyls, attenuated the reduction of SOD and GSH-Px activities induced by CCl4 in the liver tissue. It also significantly reduced the levels IL-6 and COX-2 in the liver caused by CCl4 by inhibition of NF-kB activation. Histological results indicated that Ses significantly improved the pathological lesions of liver fibrosis. CONCLUSIONS: Ses exerted hepatoprotective effects possibly due to the antioxidant effect and suppressing the NF-kB activation.

Radiographic diagnosis of sagittal plane rotational displacement in pelvic fractures: a cadaveric model and clinical case study.

PURPOSES: Our objective was to measure the sagittal plane rotational (flexion and extension) displacement of hemipelvis radiologically and analyze the ratio of flexion and extension displacement of unstable pelvic fractures. METHODS: We used 8 cadaveric models to study the radiographic evidence of pelvic fractures in the sagittal plane. We performed pelvic osteotomy on 8 cadavers to simulate anterior and posterior pelvic ring injury. Radiological data were measured in the flexion and extension group under different angles (5°, 10°, 15°, 20°, and 25°). We retrospectively reviewed 164 patients who were diagnosed with a unilateral fracture of the pelvis. Pelvic ring displacement was identified and recorded radiographically in cadaveric models. RESULTS: The flexion and extension displacement of pelvic fractures was measured in terms of the vertical distance of fracture from the top of iliac crest to the pubic tubercle (CD) or from the top of iliac crest to the lowest point of ischial tuberosity (AB). Fifty-seven pelves showed flexion displacement and 15 showed extension displacement. Closed reduction including internal fixation and external fixation was successfully used in 141 cases (86.0 %). The success rates of closed reduction in flexion and extension displacement groups were 77 and 73 %, respectively, which were lower than in unstable pelvic ring fractures. CONCLUSIONS: The sagittal plane rotation (flexion and extension) displacement of pelvic fractures could be measured by special points and lines on the radiographs. Minimally invasive reduction should be based on clearly identified differences between the sagittal plane rotation and the vertical displacement of pelvic fractures.

Phosphoserine promotes osteogenic differentiation of human adipose stromal cells through bone morphogenetic protein signalling.

Phosphoserine has potential effectiveness as a simple substrate in preparing bone replacement materials, which could enhance bone forming ability. However, there is a need to investigate the independent effect of phosphoserine on osteogenic differentiation of human adipose stem cells (hADSCs). hADSCs were cultured in an osteogenic medium with phosphoserine. Cell proliferation was analysed by CCK8 and osteogenic differentiation was measured by alkaline phosphatase (ALP) activity, von Kossa staining and real time-polymerase chain reaction (RT-PCR). No stimulatory effect of phosphoserine on cell proliferation was noted at Days 1, 4 and 7. Deposition of calcium increased after the addition of phosphoserine. mRNA expression of type I collagen (COL-I), alkaline phosphatase (ALP), osteocalcin (OCN), Osterix, bone morphogenetic protein-2 (BMP-2) and RUNX2 increased markedly with phosphoserine treatment. The BMP-2 antagonist, noggin, and its receptor kinase inhibitors, dorsomorphin and LDN-193189, attenuated phosphoserine-promoted ALP activity. BMP-responsive and Runx2-responsive reporters were activated by phosphoserine treatment. Thus phosphoserine can promote osteogenic differentiation of hADSCs, probably by activating BMP and Runx2 pathways, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.

Cordycepin prevented IL-ß-induced expression of inflammatory mediators in human osteoarthritis chondrocytes.

PURPOSE: Cordycepin, a nucleoside derivative isolated from Cordyceps, has been reported to exert anti-inflammatory, antitumor, antidiabetic and renoprotective effects. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. This study aimed to assess the effects of cordycepin on human OA chondrocytes. METHODS: In this study, human OA chondrocytes were pretreated with cordycepin at 10, 50 or 100 µM and subsequently stimulated with interleukin-1ß (IL-1ß) (5 ng/ml) for 24 h. Production of prostaglandin E2 (PGE2) and nitric oxide (NO) were evaluated by the Griess reaction and an enzyme-linked immunosorbent assay (ELISA). Gene expression of matrix metalloproteinase (MMP)-13, IL-6, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) was measured by real-time polymerase chain reaction (PCR). MMP-13 and IL-6 proteins in culture medium were determined using cytokine-specific ELISA. Western immunoblotting was used to analyse the iNOS and COX-2 protein production in culture medium. Nuclear factor kappa-B (NF-κB) activity regulation was explored using Western immunoblotting. RESULTS: Pretreatment with cordycepin significantly inhibited the production of PGE2 and NO induced by IL-1ß. Cordycepin also significantly decreased the IL-1ß-stimulated gene expression and production of MMP-13, IL-6, iNOS and COX-2 in OA chondrocytes. Pretreatment with cordycepin attenuated IL-1ß-induced activation of NF-κB by suppressing degradation of its inhibitory protein nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α) in the cytoplasm. CONCLUSIONS: We show for the first time the anti-inflammatory activity of cordycepin in human OA chondrocytes. Thus, with this unique profile of actions, cordycepin may prove to be a potentially attractive and new therapeutic/preventive agent for OA.

Dose-dependent effects of nicotine on proliferation and differentiation of human bone marrow stromal cells and the antagonistic action of vitamin C.

A range of biological and molecular effects caused by nicotine are considered to effect bone metabolism. Vitamin C functions as a biological antioxidant. This study was to evaluate the in vitro effects of nicotine on human bone marrow stromal cells and whether Vitamin C supplementation show the antagonism action to high concentration nicotine. We used CCK-8, alkaline phosphatase (ALP) activity assay, Von Kossa staining, real-time polymerase chain reaction and Western Blot to evaluate the proliferation and osteogenic differentiation. The results indicated that the proliferation of BMSCs increased at the concentration of 50, 100 ng/ml, got inhibited at 1,000 ng/ml. When Vitamin C was added, the OD for proliferation increased. For ALP staining, we found that BMSCs treated with 50 and 100 ng/ml nicotine showed a higher activity compared with the control, and decreased at the 1,000 ng/ml. Bone morphogenetic protein-2 (BMP-2) expression and the calcium depositions decreased at 100 and 1,000 ng/ml nicotine, while the addition of Vitamin C reversed the down regulation. By real-time PCR, we detected that the mRNA expression of collagen type I (COL-I) and ALP were also increased in 50 and 100 ng/ml nicotine groups (P < 0.05), while reduced at 1,000 ng/ml (P < 0.05). When it came to osteocalcin (OCN), the changes were similar. Taken all together, it is found that nicotine has a two-phase effect on human BMSCs, showing that low level of nicotine could promote the proliferation and osteogenic differentiation while the high level display the opposite effect. Vitamin C could antagonize the inhibitory effect of higher concentration of nicotine partly.

Piperine inhibits LPS induced expression of inflammatory mediators in RAW 264.7 cells.

The aim of the present study was to investigate the effects of piperine on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved. RAW264.7 cells were pretreated with piperine at 10, 50 or 100 µg/ml and subsequently stimulated with LPS (1 µg/ml) for 24 h. We found that piperine inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO) induced by LPS. Piperine significantly decreased LPS-stimulated gene expression and production of tumor necrosis factor-alpha (TNF), inducible NO synthase (iNOS) and COX-2 in RAW264.7 cells. Piperine inhibited the LPS-mediated activation of nuclear factor-kappa B (NF-kappaB) by suppressing the degradation of inhibitor-κB proteins (IκB) and the translocations of p65 subunit of NF-kB from the cytosol to the nucleus. Our results demonstrate the anti-inflammatory activity of piperine in RAW264.7 cells; suggesting that piperine may be a potential agent in the treatment of inflammation.

Nicotine promotes proliferation and collagen synthesis of chondrocytes isolated from normal human and osteoarthritis patients.

The aims of the study were to show the direct effect of nicotine with different concentrations (0, 25, 50, and 100 ng/ml) on chondrocytes isolated from normal human and osteoarthritis patients, respectively. Microscopic observation was performed during the culture with an inverted microscope. Methyl thiazolyl tetrazolium (MTT) assay method was adopted to observe the influence of nicotine on the proliferation of chondrocytes, and real-time PCR and ELISA were used to assay the mRNA and protein expression of type II collagen and aggrecan, respectively. We discovered that the OA chondrocytes were similar to fibroblasts in shape and grow slower than normal chondrocytes. The proliferation of the two kinds of chondrocytes was increased in a concentration-dependent manner and in a time-dependent manner (P<0.05). Also, we found that the mRNA level of type II collagen were upregulated under 25-100 ng/ml nicotine doses both in the two kinds of chondrocytes compared with control. The expression of protein levels of type II collagen were synthesized in line with the increase in mRNA. No effect was observed on aggrecan synthesis with any nicotine dose. We concluded that nicotine has the same effect on both chondrocytes, obtained either from osteoarthritis patients or from normal human, and the positive effect of smoking in OA may relate to the alteration in metabolism of chondrocytes.

Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro.

PURPOSE: Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10(-7), 10(-6) and 10(-5) M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro. METHODS: BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue. RESULTS: The cell viability was not significantly impaired until up to a concentration of 10(-5) M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10(-6) M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10(-5) M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10(-7) and 10(-6) M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10(-7)-10(-5) M nicotine (P < 0.05). CONCLUSION: It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells.

PURPOSE: Many in vitro studies of the analysis of the lactoferrin (LF) effect on cells have been reported. However, no study has yet investigated the effect of LF on osteogenic differentiation of human adipose-derived stem cells (hADSCs). The aim of this study was to evaluate the effect of LF on osteogenic differentiation of human adipose stem cells. METHODS: The hADSCs were cultured in an osteogenic medium with 0, 10, 50 and 100 µg/ml LF, respectively. hADSC proliferation was analysed by Cell Counting Kit-8 (CCK-8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, von Kossa staining and real-time polymerase chain reaction (RT-PCR). RESULTS: Cell proliferation was significantly increased by LF in a dose-dependent manner from days 4 to 14. Cells cultured with 100 µg/ml LF presented a higher activity compared with the control. The deposition of calcium was increased after the addition of LF. The mRNA expression of type I collagen (COL-I), ALP, osteocalcin (OCN) and RUNX2 increased markedly as a result of LF treatment. CONCLUSIONS: We have shown for the first time that LF could promote the proliferation and osteogenic differentiation of hADSCs, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.

Coccygectomy for stubborn coccydynia.

OBJECTIVE: To evaluate the preliminary clinical outcomes of coccygectomy in patients with coccydynia after a failure of conservative treatment. METHODS: From May 2002 to January 2010, 31 patients with coccydynia were treated by coccygectomy in our department after conservative measures had failed to produce significant relief. A questionnaire, which included the extent of relief in the painful area, improvement in quality of life, intensity of pain in the sitting position, and pain score during daily activities, was used to evaluate the results. RESULTS: All patients were followed up for 1 to 6 years (mean 3.3 years). The results were excellent in 20 patients (64.5%), good in 7 patients (22.6%), moderate in 3 patients (9.7%) and poor in 1 patient (3.2%). The excellent and good rates amounted to 87.1%. All patients except one had complete resolution of their symptoms and were subjectively highly satisfied with the outcomes of the surgery. Only 2 cases of superficial infection were observed postoperatively. CONCLUSION: Coccygectomy is a feasible management option for patients with coccygodynia that has no response to conservative treatments.

K-wire and tension band wire fixation in treating sternoclavicular joint dislocation.

OBJECTIVE: To evaluate the feasibility and therapeutic effect of treating sternoclavicular joint dislocation by K-wire and tension band wire fixation, and to improve the safety and stability of this technique. METHODS: This study consisted of 9 cases, 6 males and 3 females with the mean age of 25 years (range, 9-62 years). The causes were traffic accident in 7 cases, falling in 1 case and fight in 1 case. The duration from injury to operation was 2 hours to 7 days. There were 5 left dislocations and 4 right dislocations; 8 anterior dislocations and 1 posterior dislocation, including one combined with left scapular fracture and one with left olecranon fracture. Open reduction and internal fixation using K-wires and tension band wires were performed to treat dislocations. RESULTS: All patients were followed up for 6 to 24 months, 10 months on average. According to Rockwood's rating scale on postoperative sternoclavicular joint, 8 cases achieved excellent outcomes with an average score of 13.88, and the rest case achieved a good outcome with the score of 12. Anatomical reduction was obtained in all cases. There were no such postoperative complications as severe infection, injury to blood vessel and nerve, failure of fixation, etc. Patients were all satisfied with the anatomical reduction and functional recovery. CONCLUSIONS: The technique of K-wire and tension band wire fixation is safe, simple, effective, less invasive and has been successfully used in orthopedic surgery. It is effective in treating sternoclavicular joint dislocation though it has some disadvantages.

Intramedullary nailing of clavicular midshaft fractures in adults using titanium elastic nail.

OBJECTIVE: Studies showed elastic stable intramedullary nailing (ESIN) of displaced midclavicular fractures has excellent outcomes, as well as high complication rates and specific problems. The aim was to discuss ESIN of midshaft clavicular fractures. METHODS: Totally 60 eligible patients (aged 18-63 years) were randomized to either ESIN group or non-operative group between January 2007 and May 2008. Clavicular shortening was measured after trauma and osseous consolidation. Radiographic union and complications were assessed. Function analysis including Constant shoulder scores and disabilities of the arm, shoulder and hand (DASH) scores were performed after a 15-month follow-up. RESULTS: ESIN led to a signifcantly shorter time to union, especially for simple fractures. In ESIN group, all patients got fracture union, of which 5 cases had medial skin irritation and 1 patient needed revision surgery because of implant failure. In the nonoperative group, there were 3 nonunion cases and 2 symptomatic malunions developed requiring corrective osteotomy. At 15 months after intramedullary stabilization, patients in the ESIN group were more satisfied with the appearance of the shoulder and overall outcome, and they benefited a lot from the great improvement of post-traumatic clavicular shortening. Furthermore, DASH scores were lower and Constant scores were significantly higher in contrast to the non-operative group. CONCLUSION: ESIN is a safe minimally invasive surgical technique with lower complication rate, faster return to daily activities, excellent cosmetic and better functional results, restoration of clavicular length for treating mid-shaft clavicular fractures, resulting in high overall satisfaction, which can be regard as an alternative to plate fixation or nonoperative treatment of mid-shaft clavicular fractures.

Osteogenic capability of autologous rabbit adipose-derived stromal cells in repairing calvarial defects.

OBJECTIVE: To evaluate the in vitro and in vivo osteogenic capability of adipose-derived stromal cells (ASCs). METHODS: ASCs were isolated from New Zealand white rabbits and determined by alkaline phosphatase (ALP) staining, von Kossa staining and alizarin red staining. Some specific markers of osteogenic differentiation, including ALP, osteocalcin (OCN), osteopontin (OPN) were examined by reverse transcription-polymerase chain reaction (RT-PCR). In vivo, demineralized bone matrix (DBM)-ASCs composites were implanted into the rabbit calvarial defects created at each side of the longitudinal midline. After 6 weeks, histologic properties of the transplants were analyzed. RESULTS: ASCs were successfully induced into osteogenesis. ALP staining, von Kossa staining and alizarin red staining showed positive results. The expressions of ALP, OCN and OPN were detected in ASCs after cultivation in osteogenic medium. Extensive new bone was observed in the defects transplanted with DBM-ASCs composites. CONCLUSION: ASCs have the potential to differentiate into osteogenic lineage and DBM-ASCs constructs are a promising method for regeneration in bone defects.

Decursin alleviates the aggravation of osteoarthritis via inhibiting PI3K-Akt and NF-kB signal pathway.

Osteoarthritis (OA) is a common joint disease that takes joint degeneration or aging as its pathological basis, and joint swelling, pain or dysfunction as its main clinical manifestations. Decursin (DE), the major active component isolated from Angelica gigas Nakai, has been demonstrated to possess anti-inflammatory effect in many diseases. But, the specific physiological mechanism of DE on OA is not clear yet. Therefore, the object of this study was to assess the therapeutic effect of DE on OA, and to explore its potential anti-inflammatory mechanisms. In vitro cell experiments, the inflammatory response in chondrocytes is mediated via interleukin-1ß (IL-1ß), which led to abnormal secretion of pro-inflammatory factors, such as prostaglandin E2 (PGE2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), nitric oxide (NO) and inducible nitric oxide synthase (iNOS). These cytokines were all decreased by the preconditioning of DE in a dose-dependent form of 1, 5, and 10 µM. Moreover, DE could restrain IL-1ß-mediated inflammatory reaction and the collapse of extracellular matrix (ECM) via reducing the secretion of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) and MMPs (matrix metalloproteinases). In short, DE restrained IL-1ß-mediated abnormal excitation of PI3K/AKT/NF-κB axis. Furthermore, molecular docking analysis showed that DE has a strong binding affinity with the inhibitory targets of PI3K. In vivo animal studies, DE treatment could helped to improve destruction of articular cartilage and decreased the serum inflammatory factor levels in an operationally induced mouse OA model. To sum up, these data obtained from the experiment indicate that DE has good prospects for the treatment of osteoarthritis.

Possible osteoprotective effects of myricetin in STZ induced diabetic osteoporosis in rats.

Myricetin is a flavonoid which has many pharmacological effects. However, to date there is no evidence study on the effect of myricetin in diabetic condition. This study was aimed to investigate whether myricetin could protect against diabetic osteoporosis in streptozotocin induced rats. Female Wistar rats were randomly allocated to four equal groups: diabetic group (DG), diabetic group with myricetin (50 mg per kilogram per day), (D) diabetic group with myricetin (100 mg/kg/day) and normal control group (CG). Body weight was recorded once a week. After treatment with myricetin for 12 weeks, serum biochemical analyses, the microarchitecture of femora, and histological changes were evaluated. We found that the bone mineral density (BMD) of myricetin (100 mg per kilogram per day)treatment group significantly increased than in the diabetic group (P < 0.05). The alkaline phosphatase and osteocalcin were markedly blocked in diabetic rats relative to normal control group (P < 0.05); however, the inhibition was prevented by the myricetin treatment group. Results also showed that myricetin treatment could dramatically improve trabecular bone microarchitecture through increasing bone mass such as trabecular number (Tb.N), bone volume per tissue volume (BV/TV), and decreasing that of structure model index (SMI) and trabecular separation (Tb.Sp), comparing with the control group. We also found that myricetin could significantly lower the oxidative damage and up-regulate the activity of superoxide dismutase (SOD) and catalase activity. In summary, we showed that myricetin can effectively improve abnormal bone metabolism in streptozotocin induced rats, which may provide a beneficial medicine on diabetic bone disease.

Correction to: Plumbagin Prevents IL-1ß-Induced Inflammatory Response in Human Osteoarthritis Chondrocytes and Prevents the Progression of Osteoarthritis in Mice.

The original version of this article contained mistakes, and the authors would like to correct them. The correct details are given below.

Activation of Nrf2/HO-1 signal with Myricetin for attenuating ECM degradation in human chondrocytes and ameliorating the murine osteoarthritis.

BACKGROUND: Osteoarthritis (OA), one of the prevailing joint degenerative disorders, contributes to the disability around the world. However, no effective therapeutic was introduced currently. Myricetin was reported to possess the function of anti-inflammatory, anti-diabetic and anti-cancer. Thus, we investigate the protection role of myricetin in OA progression and the potential molecular mechanism in present study. METHODS: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-13, Aggrecan, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT, Nrf2/HO-1 and nuclear factor kappa B (NF-κB) signaling pathways were analyzed by western blotting, and immunofluorescence was used to assess the expression of Nrf2, Collagen II and MMP13. The in vitro effect of myricetin was evaluated by intragastric administration into a mouse osteoarthritis model induced by destabilization of the medial meniscus. RESULTS: Myricetin not only inhibited the generation of inflammatory mediators and cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α and IL-6, but also suppressed the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in human chondrocytes under IL-1ß stimulation. Moreover, Metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5), which resulted in the degradation of cartilage, were also suppressed in chondrocytes with the treatment of myricetin. To explore the potential mechanism, we found out that myricetin suppressed NF-κB signaling pathway through Nrf2/HO-1 axis in human chondrocytes. Besides, myricetin regulated the Nrf2 signaling pathway through PI3K/Akt pathway. In addition, in vivo study demonstrated that myricetin could ameliorated the progression of OA in mice DMM model through PI3K/Akt mediated Nrf2 signaling pathway. CONCLUSION: Taken together, our data first demonstrated that myricetin possesses the therapeutic potential on OA through PI3K/Akt mediated Nrf2/HO-1 signaling pathway.

Ligustilide alleviated IL-1ß induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo.

Intervertebral disc degeneration is a multifactorial and complicated degenerative disease that imposes a huge economic burden on society. However, there is no effective treatment that can delay and reverse the progression of disc degeneration. The inflammatory response causes the death of nucleus pulposus cells and the degradation of extracellular matrix are main factors of intervertebral disc degeneration. Ligustilide is a bioactive phthalide that is said to have an anti-inflammatory effect and anti-apoptosis effect on various disorders. Therefore, we further explored the protective effect of ligustilide on intervertebral disc degeneration and its potential mechanism. In this study, we found that ligustilide inhibited apoptosis, suppressed the expression of related inflammatory mediators (iNOS and COX-2) and decreased the expression of inflammatory cytokines (TNF-a and IL-6) in nucleus pulposus cells under IL-1ß stimulation. At the same time, the degradation of extracellular matrix of nucleus pulposus cells induced by IL-1ß was inhibited. In addition, we also found that ligustilide inhibits the inflammation response by inhibiting the NF-κB signaling pathway. Moreover, TUNEL assay and histological analysis showed that ligustilide could inhibit the apoptosis of nucleus pulposus cells and ameliorate the progression of intervertebral disc degeneration in punctured Rat IDD model. In summary, ligustilide may become a new potential treatment for intervertebral disc degeneration.