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1.
Medicine (Baltimore) ; 100(38): e27316, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34559148

ABSTRACT

ABSTRACT: To summarize the surgical technique and clinical effects of the extended anterolateral approach for the treatment of Schatzker type II and Schatzker type V/VI involving the posterolateral column tibial plateau.From January 2015 through December 2018, 28 patients with tibial plateau fractures involving the posterolateral column were included in the study. Among them, 16 patients were Schatzker type II treated using an extended anterolateral approach with lateral tibial locking compression plate fixation. Twelve patients were Schatzker type V or VI treated using an extended anterolateral combined with a medial approach using lateral tibial locking compression plate plus medial locking compression plate fixation. All cases were followed up for 15 to 31 months, with an average follow-up of 22.5 ±â€Š3.7 months. During the follow-up, the tibial plateau angle (TPA), lateral posterior angle (PA) and Rasmussen radiological criteria were used to evaluate the effect of fracture reduction and fixation; the Hospital for Special Knee Surgery score and the range of motion were used to evaluate knee function. Additionally, the Lachman and knee Valgus (Varus) stress tests were used to evaluate anteroposterior and lateral stability of the knee.All fractures healed. At the 12-month follow-up, the Schatzker type II group revealed a mean TPA of 86.38 ±â€Š3.92°, a mean PA of 7.43 ±â€Š2.68°, and a mean Rasmussen radiological score of 16.00 ±â€Š2.06 points. The Schatzker type V/VI group showed a mean TPA of 84.91 ±â€Š3.51°, a mean PA of 9.68 ±â€Š4.01°, and a mean Rasmussen radiological score of 15.33 ±â€Š2.99 points. During the 1-year follow-up, when the postoperative PA was re-measured, the TPA and Rasmussen score of the 2 groups did not change significantly (P > .05). At the last follow-up, the Schatzker type II group showed a knee flexion angle of 110° to 135° and a mean HHS score of 88.37 ±â€Š10.01 points. The Schatzker type V/VI group revealed a knee flexion angle of 100° to 130° and a mean HHS score of 82.17 ±â€Š10.76 points. Additionally, up to the last follow-up, the Lachman and knee Valgus (Varus) stress test results of the 2 groups were negative. No complications were found.The extended anterolateral approach is a good choice to treat tibial plateau fractures involving the posterolateral column.


Subject(s)
Fracture Fixation, Internal/methods , Knee Injuries/surgery , Tibial Fractures/surgery , Adult , Aged , Female , Fracture Fixation, Internal/statistics & numerical data , Humans , Knee Injuries/diagnostic imaging , Male , Middle Aged , Radiography , Recovery of Function , Retrospective Studies , Tibial Fractures/diagnostic imaging
2.
Cell Death Dis ; 11(10): 846, 2020 10 12.
Article in English | MEDLINE | ID: mdl-33046704

ABSTRACT

Vital osteocytes have been well known to function as an important orchestrator in the preservation of robustness and fidelity of the bone remodeling process. Nevertheless, some key pathological factors, such as sex steroid deficiency and excess glucocorticoids, and so on, are implicated in inducing a bulk of apoptotic osteocytes, subsequently resulting in resorption-related bone loss. As much, osteocyte apoptosis, under homeostatic conditions, is in an optimal state of balance tightly controlled by pro- and anti-apoptotic mechanism pathways. Importantly, there exist many essential signaling proteins in the process of osteocyte apoptosis, which has a crucial role in maintaining a homeostatic environment. While increasing in vitro and in vivo studies have established, in part, key signaling pathways and cross-talk mechanism on osteocyte apoptosis, intrinsic and complex mechanism underlying osteocyte apoptosis occurs in various states of pathologies remains ill-defined. In this review, we discuss not only essential pro- and anti-apoptotic signaling pathways and key biomarkers involved in these key mechanisms under different pathological agents, but also the pivotal role of apoptotic osteocytes in osteoclastogenesis-triggered bone loss, hopefully shedding new light on the attractive and proper actions of pharmacotherapeutics of targeting apoptosis and ensuing resorption-related bone diseases such as osteoporosis and fragility fractures.


Subject(s)
Bone Diseases/metabolism , Osteocytes/metabolism , Apoptosis , Humans , Signal Transduction
3.
Aging (Albany NY) ; 12(13): 13477-13487, 2020 07 13.
Article in English | MEDLINE | ID: mdl-32661199

ABSTRACT

Induced osteogenesis of adipose-derived mesenchymal stem cells (AMSCs) has been used to facilitate bone regeneration. Specifically, hydrostatic pressure (HP) has been implicated as a key regulator of AMSC differentiation, whereas the mechanisms that underlie the effects of HP on osteogenesis of AMSCs are not fully understood. Long noncoding RNAs (lncRNAs) are emerging regulators for osteogenic differentiation from AMSCs. In the current study, we found that lncRNA-PAGBC was a specific lncRNA that significantly upregulated during osteogenic differentiation of AMSCs based on published database. HP increased lncRNA-PAGBC, which is a competitive endogenous RNA (ceRNA) that binds to the osteogenesis-inhibitory microRNA, miR-133b, to regulate osteogenic differentiation of AMSCs. Moreover, a key osteogenesis-trigger gene, runt-related transcription factor 2 (RUNX2), was identified as a target gene for miR-133b. Suppression of RUNX2 by miR-133b caused impaired osteogenic differentiation of AMSCs. Furthermore, lncRNA-PAGBC overexpression upregulated, whereas lncRNA-PAGBC silencing decreased the expression of RUNX2 through miR-133b. Together, these data suggest that HP induces osteogenic differentiation of AMSCs through increasing lncRNA-PAGBC.


Subject(s)
Cell Differentiation/genetics , Core Binding Factor Alpha 1 Subunit/genetics , Mesenchymal Stem Cells/physiology , MicroRNAs/metabolism , Osteogenesis/genetics , RNA, Long Noncoding/metabolism , Adipose Tissue/cytology , Adult , Cells, Cultured , Computational Biology , Gene Silencing , Healthy Volunteers , Humans , Hydrostatic Pressure , Male , Primary Cell Culture , RNA, Long Noncoding/genetics , Up-Regulation
4.
Int J Nanomedicine ; 15: 2403-2417, 2020.
Article in English | MEDLINE | ID: mdl-32308391

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Ketones/chemistry , Magnesium Silicates/chemistry , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Animals , Apatites/chemistry , Benzophenones , Body Fluids/drug effects , Cell Adhesion/drug effects , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Hydrophobic and Hydrophilic Interactions , Mesenchymal Stem Cells/drug effects , Microbial Sensitivity Tests , Polymers , Rats , Sulfonic Acids/chemistry , Surface Properties
5.
J Orthop Surg Res ; 13(1): 180, 2018 Jul 20.
Article in English | MEDLINE | ID: mdl-30029657

ABSTRACT

BACKGROUND: Currently, there remains a lack of consensus regarding factors predictive of complication such as re-nonunion after primary revision in femoral shaft nonunion subsequent to failed intramedullary nailing (IMN). A better understanding of prognostic factors could potentially reduce the risk of re-nonunion happening and allow patients to maximize their recovery in the most expeditious manner. Our study aims to identify risk factors in the development of re-nonunion after primary revision inclusive of exchanging reamed nailing (ERN) and augmentative compression plating (ACP) with IMN in situ for femoral shaft nonunion subsequent to failed IMN. METHODS: A retrospective study was performed for 63 cases (61 patients) of femoral shaft nonunion subsequent to failed IMN, who were made primary revision with either ERN or ACP from June 2007 to June 2015. The following set of variables was selected based on the speculation that they would contribute to the outcome: sex (male or female), age, body mass index(BMI), smoking, alcohol abuse, cause of injury, fracture type, type of IMN (antegrade or retrograde), use of IMN locking screws(dynamic or static), site of nonunion, primary nonunion time, pathological type of nonunion, bone defect (mm), primary revision method (ERN or ACP), and adjuvant autogenous bone grafting (ABG) (yes or no). Univariate analysis and multiple regression were used to identify risk factors in the development of re-nonunion after primary revision with either ERN or ACP for femoral shaft nonunion subsequent to failed IMN. The minimum follow-up time was 1.5 years (standard deviation [SD] = 1.2, range 1.5-8 years). RESULTS: Of 63 cases (61 patients) of femoral shaft nonunion subsequent to failed IMN, primary revision with ERN was performed in 33 (52.4%) cases and primary revision with ACP was performed in 30 (47.6%) cases. Adjuvant ABG procedure was undertaken in 39 (61.9%) cases during primary revisions. Re-nonunion was diagnosed as in 18 (28.6%) cases after primary revision with either ERN or ACP. There was a significant difference in time to union between patients treated with primary ERN and those with primary ACP (log-rank, p = 0.006). Furthermore, the difference was also statistically significant between patients with adjuvant ABG procedure and those without it (log-rank, p = 0.009). The relative risk factors included smoking, BMI, site of nonunion, bone defect, primary revision method, and adjuvant ABG procedure. However, primary revision method and adjuvant ABG procedure were shown to be two independent risk factors in multiple logistic regression analysis. CONCLUSIONS: Patients with excessive tobacco use, BMI ≥ 30 kg/m2, bone defect ≥ 5 mm, primary revision with ERN, and no adjuvant ABG procedure had a higher likelihood of developing re-nonunion. Of these risk factors, primary revision with ERN and no adjuvant ABG procedure were two strongest risk factors.


Subject(s)
Femoral Fractures , Fracture Fixation, Intramedullary , Fractures, Ununited , Adolescent , Adult , Aged , Bone Nails , China , Female , Femoral Fractures/surgery , Fractures, Ununited/surgery , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
6.
Exp Ther Med ; 16(1): 394-399, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29896265

ABSTRACT

The aim of the present study was to compare the efficacy and complications of two fixation techniques, namely dynamic hip screw (DHS) and proximal femoral nail antirotation (PFNA), in the treatment of osteoporotic femoral intertrochanteric fracture in elderly patients, and to detect changes in transforming growth factor ß2 (TGF-ß2) expression in the two groups. A total of 100 elderly patients with femoral intertrochanteric fracture were randomly divided into two groups that were treated with either DHS or PFNA. Peri-operative complications were observed in the patients and ELISA was used to detect TGF-ß2 expression levels at 1, 7, 15 and 30 days after surgical treatment. The clinical efficacy and the incidence rate of complications at 3 months after the operation were compared. In comparison with the DHS group, the PFNA group had a shorter operation time, a lower bleeding volume and a shorter post-operative weight-bearing time. The contents of TGF-ß2 in the two groups at 7 days after the operation were higher than those at 1 day, reached a peak at 15 days and had gradually decreased again at 30 days after the operation. The contents of TGF-ß2 at 1, 7 and 15 days in the PFNA group were higher than those at the identical time-points in the DHS group (P<0.01). Regarding the clinical efficacy in the two groups at 3 months of post-surgery, the rate of excellent/good efficacy in the PFNA fixation group (90.0%) was higher than that in the DHS fixation group (74.0%). Of note, PFNA fixation had a higher clinical efficacy, a shorter operation time, less intra-operative trauma, a relatively faster fracture healing process and fewer complications in comparison with DHS fixation, and is therefore more suitable for treating osteoporotic femoral intertrochanteric fracture in the elderly. PFNA fixation is superior to DHS fixation, which may be associated with the higher level of TGF-ß2 expression in comparison with that in the DHS group.

7.
RSC Adv ; 8(34): 18745-18756, 2018 May 22.
Article in English | MEDLINE | ID: mdl-35539669

ABSTRACT

Bioactive and degradable scaffolds of nano magnesium silicate (n-MS)/zein (ZN)/poly(caprolactone) (PCL) ternary composites were prepared by 3D-printing method. The results showed that the 3D-printed scaffolds possessed controllable pore structure, and pore morphology, pore size, porosity and pore interconnectivity of the scaffolds can be efficiently adjusted. In addition, the apatite-mineralization ability of the scaffolds in simulated body fluids was obviously improved with the increase of ZN content, in which the scaffold with 20 w% ZN (C20) possessed excellent apatite-mineralization ability. Moreover, the degradability of the scaffolds was significantly enhanced with the increase of ZN content in the scaffolds. The degradation of ZN produced acidic products that could neutralize the alkaline products from the degradation of n-MS, which avoid the increase of pH value in degradable solution. Furthermore, the MC3T3-E1 cells responses (e.g. proliferation and differentiation, etc.) to the scaffolds were significantly promoted with the increase of ZN content. The in vivo osteogenesis of the scaffolds implanted the femur defects of rabbits was investigated by micro-CT and histological analysis. The results demonstrated that the new bone formation was significantly enhanced with the increase of ZN content, in which the C20 scaffold induced the highest new bone tissues, indicating excellent osteogenesis. The results suggested that the ZN in the ternary composite scaffolds played key roles in assisting bone regeneration in vivo.

8.
Biosci Rep ; 36(5)2016 10.
Article in English | MEDLINE | ID: mdl-27638499

ABSTRACT

Ulinastatin, a urinary trypsin inhibitor (UTI), is widely used to clinically treat lipopolysaccharide (LPS)-related inflammatory disorders recently. Adherent pathogen-associated molecular patterns (PAMPs), of which LPS is the best-studied and classical endotoxin produced by Gram-negative bacteria, act to increase the biological activity of osteopedic wear particles such as polymethyl-methacrylate (PMMA) and titanium particles in cell culture and animal models of implant loosening. The present study was designed to explore the inhibitory effect of UTI on osteoclastogenesis and inflammatory osteolysis in LPS/PMMA-mediated Raw264.7 cells and murine osteolysis models, and investigate the potential mechanism. The in vitro study was divided into the control group, LPS-induced group, PMMA-stimulated group and UTI-pretreated group. UTI (500 or 5000 units/ml) pretreatment was followed by PMMA (0.5 mg/ml) with adherent LPS. The levels of inflammatory mediators including tumour necrosis factor-α (TNF-α), matrixmetallo-proteinases-9 (MMP-9) and interleukin-6 (IL-6), receptor activation of nuclear factor NF-κB (RANK), and cathepsin K were examined and the amounts of phosphorylated I-κB, MEK, JNK and p38 were measured. In vivo study, murine osteolysis models were divided into the control group, PMMA-induced group and UTI-treated group. UTI (500 or 5000 units/kg per day) was injected intraperitoneally followed by PMMA suspension with adherent LPS (2×108 particles/25 µl) in the UTI-treated group. The thickness of interfacial membrane and the number of infiltrated inflammatory cells around the implants were assessed, and bone mineral density (BMD), trabecular number (Tb.N.), trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), relative bone volume over total volume (BV/TV) of distal femur around the implants were calculated. Our results showed that UTI pretreatment suppressed the secretion of proinflammatory cytokines including MMP-9, IL-6, TNF-α, RANK and cathepsin K through down-regulating the activity of nuclear factor kappa B (NF-κB) and MAPKs partly in LPS/PMMA-mediated Raw264.7 cells. Finally, UTI treatment decreased the inflammatory osteolysis reaction in PMMA-induced murine osteolysis models. In conclusion, these results confirm the anti-inflammatory potential of UTI in the prevention of particle disease.


Subject(s)
Glycoproteins/administration & dosage , Inflammation/drug therapy , Osteoclasts/drug effects , Osteogenesis/drug effects , Osteolysis/drug therapy , Animals , Cell Differentiation/drug effects , Inflammation/chemically induced , Inflammation/pathology , Lipopolysaccharides/toxicity , Mice , Mitogen-Activated Protein Kinase Kinases/biosynthesis , NF-kappa B/biosynthesis , Osteolysis/chemically induced , Osteolysis/pathology , Pathogen-Associated Molecular Pattern Molecules , RAW 264.7 Cells , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/biosynthesis
9.
Acta Orthop Traumatol Turc ; 50(4): 393-9, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27449592

ABSTRACT

OBJECTIVE: To explore the indications and efficacy of augmentative locking compression plate (LCP) or less invasive stabilization system (LISS)with autogenous bone grafting (BG) in treating distal femoral nonunion subsequent to failed retrograde intramedullary nailing (RIN). METHODS: A retrospective study was performed for 21 patients with distal femoral nonunion subsequent to failed RIN, who received therapy with either augmentative LCP (n = 11) or LISS with autogenous BG (n = 13). Operation time, time to union, union rate, time to renonunion, complication rate and SF-36 scores a year after hardware removal were compared between the two groups. RESULTS: The bone union occurred in 13/13 (100%) cases in augmentative LISS group versus 9/11 (81.8%) cases in augmentative LCP group [odds ratio (OR) = 3.21, 95% confidence interval (CI) 0.7-13]. Time to union, time to renonunion, complication rate of the augmentative LCP group were significantly more than that of the augmentative LISS with autogenous BG group (p = 0.023, p = 0.021 and p = 0.033). No significant difference was found in the average operation time of two groups (p = 0.121). At the follow-up a year after hardware removal, statistically significant HRQOL improvement in the augmentive LISS group was measured at the level of pain (p = 0.003) and general health perception (p = 0.011), as compared to the augmentive LCP group. CONCLUSIONS: We suggest augmentative LCP, for distal femoral nonunios after RIN, may be optimal for that of typeAO33A fractures, whereas augmentative LISS for that of typeAO33C fractures more.


Subject(s)
Bone Plates , Bone Transplantation/methods , Femoral Fractures/surgery , Fracture Fixation, Intramedullary , Fractures, Ununited/surgery , Postoperative Complications/surgery , Adult , Female , Humans , Male , Middle Aged , Operative Time , Retrospective Studies , Severity of Illness Index , Transplantation, Autologous , Treatment Outcome , Young Adult
10.
Clin Rheumatol ; 35(4): 973-85, 2016 Apr.
Article in English | MEDLINE | ID: mdl-25501632

ABSTRACT

Genetic factors have been shown to be of great importance for the pathogenesis of bone diseases, such as fracture, osteoporosis (OP), and osteoarthritis (OA). However, published studies on the correlations of transforming growth factor-ß1 (TGF-ß1) gene polymorphisms with bone diseases have been hampered by small sample sizes or inconclusive findings. We hence aimed at examining the relationships between a single nucleotide polymorphism in the TGF-ß1 gene (rs1982073 C>T) with bone fracture, OP, and OA risks in this meta-analysis. A systematic electronic search of literature was conducted to identify all published studies in English or Chinese on the association between the TGF-ß1 gene and fracture, OP, or OA risks. Data were abstracted independently by two reviewers. To investigate the strength of this relationship, crude odds ratios with 95 % confidence intervals were used. An updated meta-analysis based on nine independent case-control studies were chosen (patients with fracture, OP, or OA = 1569; healthy controls = 1638). Results identified a higher frequency of rs1982073 C>T in patients with fracture, OP, or OA than in healthy controls. Ethnicity and genotyping method-stratified analysis under both models implied that the rs1982073 C>T polymorphism was positively correlated with the risk of fracture, OP, and OA among Asians under detection via the non-PCR-RFLP method. Disease-stratified results yielded that rs1982073 C>T may increase the risk of fracture, OP, and OA under the allele model, but was only significantly related to OP under the dominant model. According to the sample size-stratified analysis, subjects with the rs1982073 C>T polymorphism in the allele model were more likely to develop the three bone diseases in both the small and large sample size groups, and only in the large sample size under the dominant model. Our findings show that TGF-ß1 rs1982073 C>T has a modest effect in increasing susceptibility to bone fracture, OP, and OA.


Subject(s)
Fractures, Bone/genetics , Osteoarthritis/genetics , Osteoporosis/genetics , Osteoporotic Fractures/genetics , Polymorphism, Single Nucleotide , Transforming Growth Factor beta1/genetics , Adult , Aged , Alleles , Case-Control Studies , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Odds Ratio , Polymorphism, Restriction Fragment Length , Quality Control , Risk Factors , Treatment Outcome
11.
Acta Orthop Traumatol Turc ; 49(6): 668-75, 2015.
Article in English | MEDLINE | ID: mdl-26511695

ABSTRACT

OBJECTIVE: The purpose of this study was to compare the outcomes of exchanging reamed nailing (ERN) and augmentative compression plating (ACP) with autogenous bone grafting (BG) for the treatment of aseptic femoral shaft nonunion secondary to the treatment of intramedullary nailing (IMN). METHODS: A multicenter retrospective study was performed for 178 patients (180 cases) of aseptic femoral shaft nonunion secondary to first treatment of IMN. All cases were fixed with either ERN (n=87) or ACP (n=93). In the ERN group, 42 cases (48.3%) were nonisthmal nonunions and 45 (51.7%) were isthmal nonunions. In the ACP group, 46 cases (49.5%) were nonisthmal nonunions, and 47 (50.5%) were isthmal nonunions. Operation time, blood loss, time to union, union rate, volume of drainage, time to renonunion, and complication rate were compared between the 2 groups. RESULTS: All patients were followed up, with a mean period of 4.1 years (range: 1-7.1 years). Bone union occurred in 93/93 cases (100%) in the ACP group versus 75/87 cases (86.2%) in the ERN group (odds ratio [OR]=3.28, 95% confidence interval [CI] 0.8-14). Of the 12 cases involved with renonunion in the ERN group, 10 were nonisthmal nonunions, and 2 were isthmal nonunions with cortical bone defect >3 cm. The union time, blood loss, and complication rate of the ERN group were significantly higher than those of the ACP group (p=0.028, p=0.035, and p=0.021, respectively). No significant difference was found in the average operation time of the 2 groups (p=0.151). However, for the nonisthmal nonunions, a significant difference was found between the ERN and ACP groups (p=0.018). CONCLUSION: ACP with autogenous BG can obtain a higher bone union rate and shorter time to union than ERN in the treatment of aseptic femoral shaft nonunion after failed IMN. Especially for nonisthmal femoral shaft nonunions or isthmal nonunions with larger bone defects, ACP with autogenous BG can be more advantageous than ERN for patients. A future prospective observational study should be conducted.


Subject(s)
Bone Transplantation/methods , Diaphyses/surgery , Femoral Fractures/surgery , Fracture Fixation, Internal/methods , Fracture Fixation, Intramedullary/methods , Fractures, Ununited/surgery , Adult , Female , Fracture Healing , Humans , Male , Middle Aged , Operative Time , Retrospective Studies , Treatment Outcome
12.
J Steroid Biochem Mol Biol ; 154: 237-44, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26187146

ABSTRACT

G protein-coupled estrogen receptor 30 (GPR30) is expressed in bone tissue. However, little is known regarding the function of GPR30 in postmenopausal osteoporosis. In this study, we examined the effects of GPR30 on ovariectomy (OVX)-induced osteoporosis in rats, including the effects on proliferation, differentiation, and expression of proteins in osteoblasts. Administration of G1 (35 µg/kg, ip, 3 times/week for 6 weeks), a specific agonist of GPR30, prevented OVX-induced increase in bone turnover rate, decrease in bone mineral content and bone mineral density, damage to bone structure, and aggravation of bone biomechanical properties. In addition, G1 did not affect uterine weight in the OVX rats. Osteoblasts isolated from calvarias from newborn rats were used to explore the underlying mechanisms. G1 (150 pM) promoted proliferation and differentiation of osteoblasts through a positive feedback of GPR30, which then activated the PI3K-Akt, ERK, and CREB pathways. G15 (750 pM), a specific antagonist of GPR30, reversed the above effects initiated by G1 treatment. In conclusion, activation of GPR30 protected bones against osteoporosis in OVX rats and exerted no untoward effect on the uterus. We suggest that GPR30 can be used as an effective therapeutic target for the prevention and treatment of postmenopausal osteoporosis.


Subject(s)
Bone and Bones/physiology , Ovariectomy , Receptors, G-Protein-Coupled/physiology , Animals , Animals, Newborn , Cell Proliferation/physiology , Cells, Cultured , Female , Organ Size , Osteoblasts/cytology , Osteoblasts/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Uterus
13.
Biosci Rep ; 35(4)2015 Jul 03.
Article in English | MEDLINE | ID: mdl-26181370

ABSTRACT

Identified and cloned in 1996 for the first time, G protein-coupled oestrogen receptor (ER) 30 (GPR30/GPER) has been a hot spot in the field of sex hormone research till now. In the present study, we examined the effects of low-dose oestradiol (E2) combined with G15, a specific antagonist of GPR30 on ovariectomy (OVX)-induced osteoporosis in rats. Female Sprague-Dawley (SD) rats undergoing OVX were used to evaluate the osteoprotective effect of the drugs. Administration of E2 [35 µg/kg, intraperitoneally (ip), three times/week) combining G15 (160 µg/kg, ip, three times/week) for 6 weeks was found to have prevented OVX-induced effects, including increase in bone turnover rate, decrease in bone mineral content (BMC) and bone mineral density (BMD), damage of bone structure and the aggravation in biomechanical properties of bone. The therapeutic effect of these two drugs in combination was better than that of E2 alone. Meanwhile, the administration of G15 prevented body weight increase or endometrium proliferation in the rats. In conclusion, administration of low-dose E2 combining G15 had a satisfactory bone protective effect for OVX rats, without significant influence on body weight or the uterus. This combination therapy may be an effective supplement of drugs in prevention and treatment for postmenopausal osteoporosis.


Subject(s)
Benzodioxoles/pharmacology , Estradiol/pharmacology , Osteoporosis/drug therapy , Quinolines/pharmacology , Receptors, G-Protein-Coupled/antagonists & inhibitors , Animals , Drug Therapy, Combination/methods , Female , Osteoporosis/metabolism , Ovariectomy , Rats , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled/metabolism
14.
Int J Clin Exp Pathol ; 8(3): 3198-203, 2015.
Article in English | MEDLINE | ID: mdl-26045840

ABSTRACT

Osteosarcoma (OS) is the most frequent histological form of primary bone cancer in adolescence. TP53 is a tumor suppressor gene which is essential for regulating cell division and preventing tumor formation. The purpose of this study is to examine whether genetic mutations in the TP53 gene are associated with OS risk and survival in a Chinese population. Five polymorphisms in the TP53 gene were selected in a case-control study, including 210 OS patients and 420 cancer-free controls. We found that subjects carrying rs12951053 CC genotype and rs1042522 GG genotype were significantly associated with risk of OS [odds ratio (OR)=1.68, 95% confidence intervals (CI): 1.05-2.68; OR=1.89, 95% CI: 1.16-3.07] compared with subjects carrying the common genotypes. Results of haplotype analysis also showed that A-G-G-A-C haplotype (rs12951053, rs1042522, rs8064946, rs9895829 and rs12602273) conferred significant decreased risk of OS (OR=0.37, 95% CI: 0.19-0.72) compared with A-C-G-A-C haplotype. Besides, rs1042522 was an independent prognostic factor for OS with hazard radio (HR)=1.94 (95% CI: 1.03-3.65) in GG genotype than in CC genotype. Our data suggest that genetic mutations in the TP53 gene are associated with risk and survival of OS in Chinese population.


Subject(s)
Asian People/genetics , Bone Neoplasms/genetics , Genetic Predisposition to Disease/genetics , Osteosarcoma/genetics , Polymorphism, Single Nucleotide , Tumor Suppressor Protein p53/genetics , Adolescent , Adult , Bone Neoplasms/mortality , Case-Control Studies , Child , Female , Genotype , Humans , Male , Osteosarcoma/mortality , Polymerase Chain Reaction , Proportional Hazards Models , Survival Analysis , Young Adult
15.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 21(12): 1290-4, 2007 Dec.
Article in Chinese | MEDLINE | ID: mdl-18277667

ABSTRACT

OBJECTIVE: To investigate the therapeutic effects and the related factors during operation of the less invasive stabilization system-distal femur (LISS-DF)for Types 33A3, C2 and C3 fractures classfied on the criteria by Association of Orthopedics (AO). METHODS: From August 2004 to December 2005, 26 patients with distal femoral fractures were surgically treated by LISS-DF, including 9 patients with Type 33A3, 11 with Type 33C2, and 6 with Type 33C3. There were 15 males and 11 females, aged 32-72 years (average, 55 years). The fractures occurred on the left side in 16 patients and on the right side in 10 patients. The fractures resulted from a road traffic accident in 12 patients, a fall from the height in 9, and a crush injury in 5. Of the 26 patients, 3 had an open fracture (2 Gustilo Type I, 1 Gustilo Type II A), with the mean time between the injury and the operation of 4 days (range, 6 h-16 d). The operation through a lateral para-patellar incision and a trans-articular retrograde plate of osteosynthesis (TARPO) was performed on 17 patients for Type 33C2 and 33C3 fracture of the distal femur. The locking head screw (LHS) insertion through the stab incisions and monocortical fixation was performed on 9 patients for Type 33A3 fracture. RESULTS: The follow-up of all the patients for 12-26 months averaged 14.5 months revealed that the bone union was completed in all the 26 patients, 1 of whom had a delayed bone union. The X-ray films showed that the time for the bone union was 11-36 weeks averaged 16.1 weeks, and the time for the full weight loading was 13-26 weeks averaged 17.6 weeks. Superficial infection developed in 1 patient, and the infection was cured after the dressing changes. The internal fixator attachment was performed on 5 patients 6-13 months after operation, who had a serious pain in the lateral part of the distal femur. No deep infection, loosening of the internal fixation, breakage or failure of the implants was found in all the patients. Evaluated by the Merchant score system for the knee joint, of the 26 patients 13 achieved an excellent result, 11 achieved a good result, and 2 achieved a fair result, with 92.3% excellent and good results. Based on the Rasmussen criteria for the fracture reduction, the 26 patients had standard scores of 12-19 with an average of 17.6; of the 26 patients, 16 had an excellent result, 9 had a good result, and 1 had a fair result. CONCLUSION: The LISS is consistent with the principles of biological osteosynthesis on the design, and the system offers a new and effective internal fixation method for treatment of AO Types A3, C2 and C3 fractures. However, its operation indications and operating instructions should be strictly followed.


Subject(s)
Femoral Fractures/surgery , Fracture Fixation, Internal/methods , Fractures, Open/surgery , Minimally Invasive Surgical Procedures , Adult , Aged , Bone Plates , Bone Screws , Female , Femoral Fractures/classification , Follow-Up Studies , Fracture Fixation, Internal/instrumentation , Fracture Healing , Humans , Male , Middle Aged , Plastic Surgery Procedures/methods , Tibial Fractures/surgery , Treatment Outcome
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