StemRegenin 1 attenuates the RANKL-induced osteoclastogenesis via inhibiting AhR-c-src-NF-κB/p-ERK MAPK-NFATc1 signaling pathway.

The aryl hydrocarbon receptor (AhR) pathway may play an important role in the regulation of osteoclasts, but there are still conflicting studies on this aspect, and the specific mechanism of action has not been fully elucidated. Therefore, we conducted this study to find a drug to treat osteoporosis that targets AhR. We found that StemRegenin 1 inhibited RANKL-induced osteoclastogenesis in a concentration-dependent and time-dependent manner. Through further experiments, we found that SR1 can inhibit nuclear transcription of AhR and inhibit c-src phosphorylation, and ultimately regulates the activation of the NF-κB and p-ERK/mitogen-activated protein kinase pathways. Therefore, for the first time, we discovered the way in which the AhR-c-src-NF-κB/p-ERK MAPK-NFATc1 signaling pathway regulates the expression of osteoclast differentiation-associated proteins. Finally, SR1 was shown to successfully reverse bone loss in OVX mice. These studies provide us with ideas for finding new way to treat osteoporosis.

Circular RNA circARPC1B functions as a stabilisation enhancer of Vimentin to prevent high cholesterol-induced articular cartilage degeneration.

BACKGROUND: Osteoarthritis (OA) is a prevalent and debilitating condition, that is, directly associated with cholesterol metabolism. Nevertheless, the molecular mechanisms of OA remain largely unknown, and the role of cholesterol in this process has not been thoroughly investigated. This study aimed to investigate the role of a novel circular RNA, circARPC1B in the relationship between cholesterol and OA progression. METHODS: We measured total cholesterol (TC) levels in the synovial fluid of patients with or without OA to determine the diagnostic role of cholesterol in OA. The effects of cholesterol were explored in human and mouse chondrocytes in vitro. An in vivo OA model was also established in mice fed a high-cholesterol diet (HCD) to explore the role of cholesterol in OA. RNAseq analysis was used to study the influence of cholesterol on circRNAs in chondrocytes. The role of circARPC1B in the OA development was verified through circARPC1B overexpression and knockdown. Additionally, RNA pulldown assays and RNA binding protein immunoprecipitation were used to determine the interaction between circARPC1B and Vimentin. CircARPC1B adeno-associated virus (AAV) was used to determine the role of circARPC1B in cholesterol-induced OA. RESULTS: TC levels in synovial fluid of OA patients were found to be elevated and exhibited high sensitivity and specificity as predictors of OA diagnosis. Moreover, elevated cholesterol accelerated OA progression. CircARPC1B was downregulated in chondrocytes treated with cholesterol and played a crucial role in preserving the extracellular matrix (ECM). Mechanistically, circARPC1B is competitively bound to the E3 ligase synoviolin 1 (SYVN1) binding site on Vimentin, inhibiting the proteasomal degradation of Vimentin. Furthermore, circARPC1B AAV infection alleviates Vimentin degradation and OA progression caused by high cholesterol. CONCLUSIONS: These findings indicate that the cholesterol-circARPC1B-Vimentin axis plays a crucial role in OA progression, and circARPC1B gene therapy has the opportunity to provide a potential therapeutic approach for OA.

Relationship between acrylamide and glycidamide hemoglobin adduct levels and osteoarthritis: a NHANES analysis.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, and acrylamide is a chemical produced when foods are processed at high temperatures. Recent epidemiological research linked acrylamide exposure from the diet and environment to a number of medical disorders. However, whether acrylamide exposure is associated with OA is still uncertain. This study was aimed at assessing the relationship between OA and hemoglobin adducts of acrylamide and its metabolite glycidamide (HbAA and HbGA). Data were taken from four cycles of the US NHANES database (2003-2004, 2005-2006, 2013-2014, 2015-2016). Individuals aged between 40 and 84 years who had complete information on arthritic status as well as HbAA and HbGA levels were eligible for inclusion. Univariate and multivariate logistic regression analysis s was performed to determine associations between study variables and OA. Restricted cubic splines (RCS) were used to examine non-linear associations between the acrylamide hemoglobin biomarkers and prevalent OA. A total of 5314 individuals were included and 954 (18%) had OA. After adjusting for relevant confounders, the highest quartiles (vs. lowest) of HbAA (adjusted odds ratio (aOR) = 0.87, 95% confidence interval (CI), 0.63-1.21), HbGA (aOR = 0.82, 95% CI, 0.60-1.12), HbAA + HbGA (aOR = 0.86, 95% CI, 0.63-1.19), and HbGA/HbAA (aOR = 0.88, 95% CI, 0.63--1.25) were not significantly associated with greater odds for OA. RCS analysis revealed that HbAA, HbGA, and HbAA + HbGA levels were non-linearly and inversely associated with OA (p for non-linearity < 0.001). However, the HbGA/HbAA ratio displayed a U-shaped relationship with prevalent OA. In conclusion, acrylamide hemoglobin biomarkers are non-linearly associated with prevalent OA in a general US population. These findings implicate ongoing public health concerns for widespread exposure to acrylamide. Further studies are still warranted to address the causality and biologic mechanisms underlying the association.

Tetrandrine inhibits RANKL-induced osteoclastogenesis by promoting the degradation of TRAIL.

BACKGROUND: Tetrandrine, a bisbenzylisoquinoline (BBI) alkaloid extracted from Stephania tetrandra (S. Moore), and is widely used in several diseases such as tuberculosis, hyperglycemia, malaria, and tumors. Tetrandrine was recently shown to prevent bone loss in ovariectomized mice. However, the specific mechanism underlying osteoclastogenesis inhibition remains unclear. METHODS: Tetrandrine's cytotoxicity to cells was determined using the Cell Counting Kit-8 assay. Tartrate-resistant acid phosphatase staining, immunofluorescence and bone resorption assay were performed to evaluate osteoclasts' differentiation and absorption capacity. The bone-forming capacity was assessed using alkaline phosphatase and Alizarin red S staining. qPCR and Western blotting were applied to assess the related genes and protein expression. Tetrandrine's impact on TRAIL was demonstrated through a co-immunoprecipitation assay. Animal experiments were performed for the detection of the therapeutic effect of Tetrandrine on osteoporosis. RESULTS: Tetrandrine attenuated RANKL-induced osteoclastogenesis and decreased the related gene expression. The co-immunoprecipitation assay revealed that Tetrandrine administration accelerated the ubiquitination of TNF-related apoptosis-inducing ligand (TRAIL), which was subsequently degraded. Moreover, TRAIL overexpression was found to partially reverse the Tetrandrine-induced inhibition of osteoclastogenesis. Meanwhile, Tetrandrine significantly inhibited the phosphorylation of p38, p65, JNK, IKBα and IKKα/ß, while the TRAIL overexpression weakened this effect. In addition, Tetrandrine promoted osteogenesis and inhibited the TRAIL expression in osteoblasts. Tetrandrine consistently improved bone destruction by stimulating bone formation and inhibiting bone resorption in an OVX-induced mouse model. CONCLUSION: Tetrandrine inhibits RANKL-induced osteoclastogenesis by promoting TRAIL degradation and promotes osteoblast differentiation, suggesting its potential in antiosteopenia pharmacotherapy.

Single-cell RNA sequencing analysis dissected the osteo-immunology microenvironment and revealed key regulators in osteoporosis.

Osteoporoticfractures become increasingly common in postmenopausal women over age 55 years and men after age 65 years, bringing about substantial bone-associated morbidities, and augmented mortality and health-care costs. Advanced researches have led to a more accurate assessment of osteoporosis (OP) and have broadened the range of therapeutic approaches available to prevent osteoporotic fractures. Single-cell RNA sequencing (scRNA-seq) analysis is an evolutionary method that quantifies the majority of transcripts in individual cells at isoform resolution, paving the way for more detailed analyses of gene regulation in biology and medicine. We have extracted 19,102 cells and 4097 dynamical genes with significant expression changes. Several new subtypes of macrophages and differentially over-expressed genes were discovered in the trajectory of osteoclasts formation. The zinc finger protein 36, C3H type-like 1 (ZFP36L1) and defensin alpha 3 (DEFA3) were identified as novel bone metabolism-related genes. RETN-CAP1 was newly found to be involved in the interaction between osteoclasts and immunocytes, indicating that osteo-immunology microenvironment substantially contributed to the pathology of osteoporosis or osteopenia. In this research, we have performed Single-cell RNA sequencing analysis to display the trajectory of osteoclast formation and reveal the possible gene targets and signaling pathways that probably play an important role in osteoporosis.

MCU Inhibitor Ruthenium Red Alleviates the Osteoclastogenesis and Ovariectomized Osteoporosis via Suppressing RANKL-Induced ROS Production and NFATc1 Activation through P38 MAPK Signaling Pathway.

Osteoporosis is a disorder of bone metabolism that is extremely common in elderly patients as well as in postmenopausal women. The main manifestation is that the bone resorption capacity is greater than the bone formation capacity, which eventually leads to a decrease in bone mass, increasing the risk of fracture. There is growing evidence that inhibiting osteoclast formation and resorption ability can be effective in treating and preventing the occurrence of osteoporosis. Our study is the first time to explore the role of the mitochondrial calcium uniporter (MCU) and its inhibitor ruthenium red (RR) in bone metabolism, clarifying the specific mechanism by which it inhibits osteoclast formation in vitro and plays a therapeutic role in osteoporosis in vivo. We verified the suppressive effects of RR on the receptor activator of nuclear factor-κB ligand (RANKL-)-induced differentiation and bone resorption function of osteoclasts in vitro. The reactive oxygen species (ROS) production stimulated by RANKL and the expression level of P38 MAPK/NFATc1 were also found to be inhibited by RR. Moreover, the promotion of RR on osteogenesis differentiation was investigated by alkaline phosphatase (ALP) and alizarin red S (ARS) staining and the detection of osteogenesis-specific gene expression levels by quantitative polymerase chain reaction (qPCR) and western blotting. Moreover, in ovariectomy (OVX-)-induced osteoporosis models, RR can downregulate the expression and function of the MCU, relieving bone loss and promoting osteogenesis to present a therapeutic effect on osteoporosis. This new finding will provide an important direction for the study of RR and MCU in the study of bone metabolism therapy targets.

Photoluminescent carbon dots (PCDs) from sour apple: a biocompatible nanomaterial for preventing UHMWPE wear-particle induced osteolysis via modulating Chemerin/ChemR23 and SIRT1 signaling pathway and its bioimaging application.

Photoluminescent nanomaterials have been widely employed in several biological applications both in vitro and in vivo. For the first time, we report a novel application of sour apple-derived photoluminescent carbon dots (PCDs) for reducing ultra-high molecular weight polyethylene (UHMWPE) wear particle-induced osteolysis using mouse calvarial model. Generally, aseptic prosthetic loosening seems to be a significant postoperative problem for artificial joints replacement, which is mainly contributed by UHMWPE-induced osteolysis. Hence, inhibiting osteoclastic bone-resorption could minimize UHMWPE-induced osteolysis for implant loosening. Prior to osteolysis studies, the prepared sour apple-derived PCDs were employed for bioimaging application. As expected, the prepared PCDs effectively inhibited the UHMWPE particle-induced osteoclastogenesis in vitro. The PCDs treatment effectively inhibited the UHMWPE-induced osteoclast differentiation, F-actin ring pattern, and bone resorption in vitro. Also, the PCDs reduced the UHMWPE-induced ROS stress as well as the expression level of pro-inflammatory cytokines, including TNF-α, IL-1, IL-6, and IL-8. Further, the qPCR and western blot results hypothesized that PCDs inhibited the UHMWPE wear particle-induced osteolysis through suppressing chemerin/ChemR23 signaling and NFATc1 pathway, along with upregulation of SIRT1 expression. Overall, these findings suggest that the synthesized PCDs could be a potential therapeutic material for minimizing UHMWPE particle-induced periprosthetic osteolysis to avoid postoperative complications.

MiR-25 overexpression inhibits titanium particle-induced osteoclast differentiation via down-regulation of mitochondrial calcium uniporter in vitro.

BACKGROUND: Mitochondrial calcium uniporter (MCU) is an important ion channel regulating calcium transport across the mitochondrial membrane. Calcium signaling, particularly via the Ca2+/NFATc1 pathway, has been identified as an important mediator of the osteoclast differentiation that leads to osteolysis around implants. The present study aimed to investigate whether down-regulation of MCU using microRNA-25 (miR-25) mimics could reduce osteoclast differentiation induced upon exposure to titanium (Ti) particles. METHODS: Ti particles were prepared. Osteoclast differentiation of RAW264.7 cells was induced by adding Ti particles and determined by TRAP staining. Calcium oscillation was determined using a dual-wavelength technique. After exposure of the cells in each group to Ti particles or control medium for 5 days, relative MCU and NFATc1 mRNA expression levels were determined by RT-qPCR. MCU and NFATc1 protein expression was determined by western blotting. NFATc1 activation was determined by immunofluorescence staining. Comparisons among multiple groups were conducted using one-way analysis of variance followed by Tukey test, and differences were considered significant if p < 0.05. RESULTS: MCU expression was reduced in response to miR-25 overexpression during the process of RAW 264.7 cell differentiation induced by Ti particles. Furthermore, osteoclast formation was inhibited, as evidenced by the low amplitude of calcium ion oscillation, reduced NFATc1 activation, and decreased mRNA and protein expression levels of nuclear factor-κB p65 and calmodulin kinases II/IV. CONCLUSIONS: Regulation of MCU expression can impact osteoclast differentiation, and the underlying mechanism likely involves the Ca2+/NFATc1 signal pathway. Therefore, MCU may be a promising target in the development of new strategies to prevent and treat periprosthetic osteolysis.

Chemerin/ChemR23 signaling mediates the effects of ultra-high molecular weight polyethylene wear particles on the balance between osteoblast and osteoclast differentiation.

BACKGROUND: Ultra-high molecular weight polyethylene (UHMWPE) is one of the favored materials for total joint replacement, but its wear particles cause osteolysis. This study aims to elucidate the signaling that mediates the effects of UHMWPE particles on bone cells. METHODS: RAW264.7 and MC3T3-E1 cells were treated with UHMWPE particles. Chemerin/ChemR23 signaling was manipulated by either overexpressing Rarres2 and Cmklr1 or silencing Cmklr1. The osteoblast and osteoclast differentiation was evaluated by Alizarin red and TRAP staining, respectively. The expression of osteogenic and osteoclastogenic markers was assessed with quantitative real time PCR and western blot. RESULTS: UHMWPE particles upregulated the expression of Rarres2 and Cmklr1 in both osteoblast and osteoclast precursor cells. UHMWPE particles induced osteoclast differentiation while inhibited osteoblast differentiation, and this effect was abrogated by silencing Cmklr1 but augmented by the overexpression of Rarres2 and Cmklr1. Similarly, the expression of osteogenic marker genes was inhibited while that of osteoclastogenic marker genes was activated by UHMWPE particles, and this effect was abolished by silencing Cmklr1 and enhanced by Rarres2 and Cmklr1 overexpression. CONCLUSIONS: These results demonstrated that chemerin/ChemR23 signaling plays a central role in the effects of UHMWPE particles on the balance of osteogenic and osteoclastogenic differentiation, which changes the course of bone remodeling and eventually results in osteolysis.

MCU-Dependent mROS Generation Regulates Cell Metabolism and Cell Death Modulated by the AMPK/PGC-1α/SIRT3 Signaling Pathway.

The mitochondrial calcium uniporter is an intensively investigated calcium channel, and its molecular components, structural features, and encoded genes have long been explored. Further studies have shown that the mitochondrial calcium unidirectional transporter (MCU) is a macromolecular complex related to intracellular and extracellular calcium regulation. Based on the current understanding, the MCU is crucial for maintaining cytosolic Ca2+ (cCa2+) homeostasis by modulating mitochondrial Ca2+ (mCa2+) uptake. The elevation of MCU-induced calcium levels is confirmed to be the main cause of mitochondrial reactive oxygen species (mROS) generation, which leads to disordered cellular metabolic patterns and cell death. In particular, in an I/R injury model, cancer cells, and adipocytes, MCU expression is maintained at high levels. As is well accepted, the AMPK/PGC-1α/SIRT3 pathway is believed to have an affinity for mROS formation and energy consumption. Therefore, we identified a link between MCU-related mROS formation and the AMPK/PGC-1α/SIRT3 signaling pathway in controlling cell metabolism and cell death, which may provide a new possibility of targeting the MCU to reverse relevant diseases.

Thermo-responsive injectable naringin-loaded hydrogel polymerised sodium alginate/bioglass delivery for articular cartilage.

In the human body, joint cartilage is of great importance. It has long been a big therapeutic problem to fix joint cartilage lesions as it appears due to different conditions. Recent stories have shown that the cartilage replacement process must delay the extracellular (ECM) cartilage deterioration and modulate the host's inflammation response. For the reconstruction of the articular cartilage, drug-loaded injectable hydrogels were developed. This hydrogel could retain the chondrocyte phenotype, but the host's inflammatory reaction could also be controlled. The bioglass (BG)/sodium alginate (SA) injectable hydrogels was combined with agarose (AG)/Naringin hydrogel in injectable thermal response for articular cartilage regeneration with a non-chargeable hydrogel that contains both Naringin and BG (Naringin-BG hydrogels). The Naringin-BG hydrogel has an adequate swelling ratio that encourages the fusion of tissue formed with host tissue and enables the gradual release of Naringin bioavailabilities enhanced in situ. The Naringin-BG hydrogel can upgrade the typical chondrocyte phenotype by upregulating aggrecan, SRY-box 9, and collagen type II alpha one chain. It may also stimulate the polarization of M2 macrophage, lower inflammations, and prevent ECM degradations through the decrease of the expressions of the indictable metalloproteinase-13 matrix, nitric oxide synthase, and metalloproteinase-1 matrix. The formed tissues were identical to normal tissues and firmly incorporated with the surrounding tissue after administering the Naringin-BG hydrogels into the rat model articular cartilage defects. Then the injectable Naringin-BG hydrogel increases the bioavailable content of Naringin and retains the chondrocyte phenotype.

Sclareol inhibits RANKL-induced osteoclastogenesis and promotes osteoblastogenesis through promoting CCN1 expression via repressing the MAPK pathway.

Osteoclasts are crucial cellular components of bone and are the cause of various bone problems like osteoporosis. Various biological activities such as anti-tumorous, anti-inflammatory, antibacterial, and immunomodulatory function are influenced by Sclareol, as a natural diterpene compound. However, studies on the effect and mechanism of Sclareol on osteoporosis are rare. In the current research, the influence of Sclareol on osteoclastogenesis and osteoblastogenesis was targeted to be discovered in ovariectomy (OVX)-induced animal models and in vitro. The expression levels of osteoclast-related genes such as c-Fos, NFATc1, and CTSK were detected by RT-qPCR and western blotting to understand the inhibition of Sclareol on the creation of osteoclast. The influence of Sclareol on osteoblastogenesis and the expression of osteoblastogenic markers were also examined. Sclareol inhibited the osteoclastogenesis caused by receptor activator of nuclear factor-κB ligand (RANKL) which promoted osteoblastogenesis through upregulating the expression of cysteine-rich protein 61 (CYR61/CCN1), which is a matricellular protein of the CCN family. The p-ERK and p-P38 protein expression levels were considerably downregulated by Sclareol. Furthermore, CCN1 overexpression partially mimicked the inhibitory effect of Sclareol, while the opposite results were obtained after CCN1 silencing. Additionally, Sclareol protected against loss of bones in an osteoporosis mouse model generated by OVX. The acquired results indicated that Sclareol represses RANKL-induced osteoclastogenesis and promotes osteoblastogenesis via promoting the expression of CCN1 by constraining the mitogen-activated protein kinase (MAPK) pathway. Our findings proposed that for the avoidance and treatment of osteoclast-linked disorders, Sclareol is a potentially effective drug. A proposed model for mediated regulation of osteoclastogenesis and osteoblastogenesis by Sclareol. The basic model of the process by which Sclareol prevents osteoclastogenesis and promotes osteoblastogenesis. Sclareol may increase the expression of CCN1 through inhibiting the MAPK pathway, thereby inhibiting osteoclast differentiation and attenuating bone resorption. Sclareol represses the expression of c-Fos, which stimulates the formation of osteoclast. In contrast, Sclareol promotes osteoblast differentiation by upregulating Runx2 expression, thereby improving the formation of bones. Consequently, Sclareol protects against loss of bones by regulating the stability of bone makeover via inhibition of bone formation and stimulation of bone resorption. Graphical Headlights 1. Sclareol represses RANKL-induced osteoclastogenesis. 2. Sclareol promotes osteoblast differentiation. 3. Sclareol inhibits the MAPK pathway through induction of CCN1. 4. Sclareol protects against bone loss by regulating the balance of bone remodeling via inhibition of bone formation and stimulation of bone resorption.

Intravenous administration of tranexamic acid in total hip arthroplasty does not change the blood coagulopathy: a prospective thrombelastography analysis.

OBJECTIVE: Despite the wide use of tranexamic acid (TXA) in the perioperative period of total hip arthroplasty (THA), whether the hemostatic state changes after the application of intravenous (IV)-TXA are still unknown. The aim of this study was to investigate whether IV administration of TXA changes the blood coagulation following primary THA via thrombelastography (TEG) analysis and conventional laboratory tests. METHODS: A total of 174 patients who underwent primary THA from September 2016 to July 2018 were selected. They were randomly divided into two groups, 86 patients with IV administration of 15 mg/kg TXA and 88 controls without TXA usage. Demographic data, TEG paremeters, d-dimer levels, fibrin degradation products, hemoglobin, hematocrit concentration, platelet, transfusion rates, perioperative blood loss, and the occurrence of deep vein thrombosis were collected. TEG and conventional laboratory tests were performed the day before operation, the first day after operation, and seventh day after operation. RESULTS: There were no differences with regard to TEG or conventional laboratory tests between the two groups (p > 0.05). The total blood loss and drain blood loss in the TXA group were significantly lower than those in the control group (p < 0.05). The transfusion rates and the volume of blood transfusion of the control group were higher than those of the TXA group (p < 0.05). CONCLUSION: The administration of IV-TXA resulted in a significant reduction in total blood loss, transfusion volumes, and transfusion rates without the increase of thromboembolic complications. Moreover, it was confirmed that TXA would not change the coagulation via the TEG analysis.

[Relationship between lower limb alignment distribution and short-term clinical results after primary total knee arthroplasty in patients with varying degrees of knee varus].

OBJECTIVE: To analyze the relationship between the distribution of lower limb alignment and short term clinical efficacy in patients with varus-type osteoarthritis after primary total knee arthroplasty (TKA). METHODS: From December 2016 to March 2018, 87 patients (101 knees) with knee osteoarthritis were treated with the first total knee arthroplasty by the same medical group, including 21 males(25 knees) and 66 females(76 knees), ranging in age from 51 to 85 years old, with a mean of (67.6±7.0) years old. According to the difference of hip knee ankle angle (HKA) after total knee arthroplasty, the patients were divided into 4 groups:neutral position group (group A), -3°≤HKA≤3°, 50 knees;slight varus group (group B), 3°< HKA<6°, 20 knees;severe varus group (group C), HKA≥6°, 20 knees;valgus group (group D), HKA<- 3°, 11 knees. The preoperative sex, age, body mass index, operative side, preoperative and postoperative knee joint activity, HSS score, KSS clinical and functional score were compared among the 4 groups, and the relationship between the force line distribution of femoral and tibial prosthesis and the recent clinical effect was compared. RESULTS: All the patients were followed up with a mean duration of(18.4±4.0) months. The range of motion of knee joint, HSS and KSS scores at the latest follow-up after operation in the 4 groups were higher than those before operation, and the difference was statistically significant (P<0.001). There were significant differences in HSS and KSS scores among the 4 groups at the latest follow up (P<0.05);and the results in group A were better than those in group C and group D (P<0.05);the results in group B were better than those in group C and group D (P< 0.05);there was no significant difference between group A and group B or group C and group D(P>0.05). There was no significant difference in knee joint activity among the 4 groups. The score of femoral prosthesis force line within ±3°was better than that of the other group (P<0.05), and the score of tibia prosthesis force line had no significant difference between within ±3° group and other group (P>0.05). CONCLUSION: The short term clinical efficacy of patients with knee varus osteoarthritis after primary total knee arthroplasty is related to the distribution of lower limbs alignment. The short-term clinical efficacy of slight inversion position can be similar to that of neutral position. The force line distribution of femoral prosthesis is related to the short term clinical efficacy after primary knee arthroplasty.

[Effect of surgeon's handedness on distribution of prosthesis during primary total knee arthroplasty].

OBJECTIVE: To evaluate the effect of the surgeon's handedness on the distribution of prosthesis during primary total knee arthroplasty (TKA). METHODS: A retrospective analysis was performed on 86 patients (100 knees) with primary TKA completed by the same right-handed surgeon between December 2016 and December 2018, including 72 cases of single knee and 14 of bilateral knees. The patients were divided into dominant group (right side) and non-dominant group (left side) according to the operating position of the surgeon and each group had 50 knees. There was no significant difference in gender, age, body mass index, disease duration, clinical diagnosis, preoperative Hospital for Special Surgery (HSS) score, and other general data between the two groups ( P>0.05). The operation time and complications were recorded in both groups. The function of knee was evaluated by HSS score. Hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), and mechanical medial proximal tibial angle (mMPTA) were measured by using X-ray film of full-length lower extremity before TKA and at 2 weeks after TKA that were used to evaluate the coronal position of the prosthesis. Posterior distal femoral angle (PDFA) and posterior proximal tibial angle (PPTA) were measured by using lateral X-ray films at 3 months after operation that were used to evaluate the sagittal position of the prosthesis. RESULTS: There was no significant difference in operation time between the two groups ( t=-1.128, P=0.262). One case of posterior tibial artery thrombosis occurred in the dominant group, and 1 case of poor healing of the incision occurred in each of the dominant group and the non-dominant group. Patients in both groups were followed up 12-34 months with an average of 22.0 months. The HSS scores at last follow-up were 87.2±4.3 in the dominant group and 86.8±5.0 in the non-dominant group. There was no significant difference between the two groups ( t=0.471, P=0.639). No complications such as periprosthetic infection, prosthetic loosening, or periprosthetic fracture occurred during follow-up. There was no significant difference in the HKA, mLDFA, and mMPTA between the two groups before and after operation ( P>0.05). The differences in the incidence of sagittal femoral prosthesis malposition and PDFA between the two groups were significant ( P<0.05); however, there was no significant difference in the PPTA, the rate of femoral prosthesis distributed in the neutral position, the incidence of over-flexed femoral prosthesis, and the incidence of anterior femoral notch ( P>0.05). CONCLUSION: The surgeon's handedness is one of the factors affecting the placement of the sagittal femoral prosthesis in primary TKA. The incidence of sagittal femoral prosthesis malposition could increase when the surgeon performs on the non-dominant side.

Modified trapdoor procedures using autogenous tricortical iliac graft without preserving the broken cartilage for treatment of osteonecrosis of the femoral head: a prospective cohort study with historical controls.

BACKGROUND: The aim of the present study was to investigate clinical and radiological outcomes of autologous tricortical iliac grafting performed through a window created at the femoral head without suturing the opened articular cartilage for the treatment of osteonecrosis of the femoral head (ONFH), called modified trapdoor procedures. MATERIALS AND METHODS: A total of 59 consecutive patients (67 hips; 36 males and 23 females) with ONFH were included in this study, which was conducted from April 2009 to March 2012. Patients' age ranged from 27 to 46 years old, with a mean age of 36.3 years. Harris hip scores (HHS) were used to evaluate hip function pre- and postoperatively. Anteroposterior and frog-position X-rays and magnetic resonance imaging (MRI) were conducted to assess lesion location, size, and ARCO stage. Clinical failure was defined as score < 80 points or treatment by total hip arthroplasty (THA). Radiographic failure was defined as a > 3 mm of collapse in the hip. This group was retrospectively matched according to the ARCO stage, extent, location, etiology of the lesion, average age, gender, and preoperative Harris hip score to a group of 59 patients (67 hips) who underwent the "light bulb" approach between March 2007 and April 2009. RESULTS: Mean follow-up was 91.2 ± 13.6 months (range, 75-115 months). Mean HHS was 91.3 ± 4.5, compared with 83.1 ± 4.5 in the "light bulb" cohort at the 6-year follow-up examination (P < 0.001). At the 6-year follow-up, for modified trapdoor procedures, five hips (8.5%) were classified as clinical failure, and three hips underwent total hip arthroplasty; seven hips were classified as (10.4%) radiographic failure. The clinical and radiographic failure of the hips treated with the modified trapdoor procedure was significantly lower compared to the hips treated with the "light bulb" procedure (P < 0.05). Survival of the joint was not significantly related to the location of the femoral head lesion between two groups; however, better clinical and radiographic results were observed in modified trapdoor procedures with size C and the ARCO stage III. CONCLUSION: The present study demonstrated superior midterm clinical results in ONFH with the use of autologous tricortical iliac block graft through a femoral head window, without suturing the opened articular cartilage. The femoral head-preserving procedure was superior compared to the "light bulb" procedure treatment in patients with postcollapse osteonecrosis and large lesion.

The Comparative Analysis of Antegrade Versus Retrograde Approach for a Failed Porous Tantalum Rod Removal During Conversion to Total Hip Arthroplasty.

BACKGROUND The failure of porous tantalum rods applied to patients with osteonecrosis of the femoral head (ONFH) has been increasingly reported during the last few years. Very few studies have reported methods for implant removal. This study aimed at comparing 2 procedures used for the removal of a failed tantalum rod during conversion to total hip arthroplasty (THA). MATERIAL AND METHODS A total of 65 patients (65 hips), who underwent THA after failed implantation of a tantalum rod between June 2007 and December 2016, were retrospectively evaluated. These patients were classified into 2 groups depending on whether the antegrade approach (removal of the tantalum rod from the tip to the butt at the lateral femoral cortex, n=27) or retrograde approach (removal of the tantalum rod from the butt at the lateral femoral cortex to the proximal tip, n=38) was used for rod extraction. These 2 groups were compared for incision length, operation time, blood loss, fracture, tantalum debris, Harris hip scores, and the presence of osteolysis and/or radiolucency. RESULTS These 2 groups did not present any significant differences in terms of Harris hip score and incision length. However, the operation time (P=0.000), blood loss (P=0.000), amount of tantalum debris (P=0.000), and presence of radiolucency (P=0.046) were greater for the retrograde approach than for the antegrade approach. CONCLUSIONS The risk of conversion to THA following failed tantalum rod implantation is high. In such cases, the antegrade procedure was found to be a simple and efficient method for removing the trabecular metal rod with the use of a trephine.

A Retrospective Study to Compare the Efficacy and Postoperative Outcome of Total Hip Arthroplasty with Internal Screw Fixation in Patients with Avascular Necrosis of the Femoral Head.

BACKGROUND This retrospective study compared the effects of total hip arthroplasty (THA) and traditional surgery using internal screw fixation for the treatment of avascular necrosis (AVN) of the femoral head. MATERIAL AND METHODS A total of 270 patients with bilateral ANFH were retrospectively analyzed. Among them, 176 underwent THA (THA group); and 94 underwent closed reduction screw fixation (traditional group).  RESULTS The mean operation time in the traditional surgery group (82.6±15.6 min) was significantly less compared with the THA group (104.8±14.2 min) (P=0.001). Intraoperative blood loss in the traditional surgery group (219.8±21.6 mL) was significantly less compared with the THA group (339.4±29.4 mL) (P=0.001). After treatment, the mean HHS score of the THA group (76.5±9.2 points) was significantly increased when compared with the traditional surgery group (61.4±10.5 points) (P=0.001). Disease recurrence rate in the THA group was significantly reduced compared with the traditional surgery group (P=0.001). The mean quality of life score of the THA group (85.5±6.4 points) was significantly higher than that of the traditional surgery group (73.4±8.8 points) (P=0.001). CONCLUSIONS Compared with closed reduction screw fixation, THA for AVN of the femoral head effectively reduced the length of hospital stay, time to recovery, and achieved an improved clinical outcome.

MicroRNA-21-5p as a novel therapeutic target for osteoarthritis.

OBJECTIVE: Growing evidence indicates that microRNAs (miRNA) play a critical role in the pathogenesis of OA, and overexpressing or silencing miRNA expression in OA models can contribute to the development of miRNA-based therapeutics. The objective of this study was to determine whether intra-articular injection of miRNA can inhibit OA progression. METHODS: The miRNA expression profile was determined in OA cartilage tissues and controls. Functional analysis of the miRNAs on extracellular matrix degradation was performed after miRNA mimic or inhibitor transfection. Luciferase reporter assays and western blotting were employed to determine miRNA targets. To investigate the functional mechanism of miR-21-5p in OA development, miR-21-5pfl/flCol2a1-CreER and wild-type mice were subject to surgical destabilization of the medial meniscus. Therapeutically, wild-type mice undergoing surgical destabilization of the medial meniscus were treated with intra-articular injection of agomir- and antagomir-21-5p. RESULTS: We found that expression of miR-21-5p was significantly up-regulated in OA cartilage tissues. The articular cartilage degradation of miR-21-5p conditional knockout mice was significantly alleviated compared with that of wild-type mice in spontaneous and destabilization of the medial meniscus models. Through gain-of-function and loss-of-function studies, miR-21-5p was shown to significantly affect matrix synthesis genes expression, and chondrocyte proliferation and apoptosis. Further, fibroblast growth factor 18 (FGF18) was identified as a target of miR-21-5p. Intra-articular injection of antagomir-21-5p significantly attenuated the severity of experimental OA. Clinically, FGF18 expression level was correlated with miR-21-5p expression and a modified Mankin scale. CONCLUSION: Our findings reveal a miRNA functional pathway important for OA development, highlighting miRNA-21-5p silencing as an attractive therapeutic regimen in future clinical trials involving patients with OA.

Anatomical study based on 3D-CT image reconstruction of the hip rotation center and femoral offset in a Chinese population: preoperative implications in total hip arthroplasty.

BACKGROUND: Several anatomical studies regarding the value of hip rotation center (HRC) and femoral offset (FO) have been performed in Western populations. However, there are a few data on hip morphological values in the Chinese population based on CT scans. This study measured the values of the hip and pelvis, especially HRC and FO, in a Chinese population and compared them with the published values obtained from Western populations. PATIENTS AND METHODS: One hundred patients (50 females and 50 males) were included in the present study, and 3D-CT reconstructions of the hip and pelvis were generated. The mean age was 51.4 ± 8.9 years and mean body mass index (BMI) was 23.5 ± 2.6 kg/m2. All the morphologic measurements were compared between genders and sides, and the relationships between different parameters were analyzed. RESULTS: The mean FO values were 38.4 ± 4.7 mm and 35.6 ± 4.4 mm for the males and females, respectively. A significant negative correlation was noted between FO and neck shaft angle (NSA) in both genders (r = - 0.262, P = 0.009 for the males, r = - 0.350, P ≤ 0.001 for the females). A significant positive correlation was found between horizontal distance (HD) and diameter of the femoral head (DFH) in both genders (r = 0.734, P ≤ 0.001 for the males, r = 0.658, P ≤ 0.001 for the females). A significant positive correlation was noted between HD and pelvic width (PW) in males (r = 0.455, P ≤ 0.001). A significant positive correlation was also noted between HD and pelvic height (PH) in males (r = 0.318, P ≤ 0.001). A significant positive correlation was observed between FO and pelvic cavity height (PCH) in males (r = 0.411, P ≤ 0.001), and a significant positive correlation was observed between VD and PCH in females (r = 0.497, P ≤ 0.001). The tip of the greater trochanter was, on average, 7.0 mm higher than the femoral head center. Relationships between DFH and pelvic morphometric parameters were also observed. CONCLUSION: The present morphological data and the relationships between them can be applied to design better ethnic-specific THA prostheses and preoperative plans.