Synovial inducible costimulator is correlated with severity in knee osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by articular cartilage loss, which afflicts many people worldwide. Knowing the disease severity can improve the recovery rate of OA. Antibody array technology was utilized for protein expression profiling of synovial fluid from eight mild knee OA patients, eight severe knee OA patients and 16 healthy persons. Subsequently, 48 mild OA patients, 56 severe OA patients and 24 healthy controls were utilized for validation by ELISA. In the protein expression profiling, inducible costimulator (ICOS) levels were markedly higher in OA patients compared with those in the healthy population, and were significantly higher in severe OA than those in mild OA. Furthermore, ICOS levels were shown to be significantly correlated with WOMAC, MRI-MOAKS and MRI-UTE-T2* scores. The multivariate logistic regression analysis indicated that higher levels of ICOS could significantly increase the risk of severe OA. Synovial ICOS levels were positively correlated with the radiographic severity of OA. ICOS may represent a biomarker for predicting the OA severity and may be involved in the development and progression of knee OA.

Osteoclasts secrete leukemia inhibitory factor to promote abnormal bone remodeling of subchondral bone in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a common chronic degenerative joint disease. At present, there is no effective treatment to check the progression of osteoarthritis. Osteochondral units are considered to be one of the most important structures affecting the occurrence and development of osteoarthritis. Osteoclasts mediate an increase in abnormal bone remodeling in subchondral bone in the early stage of osteoarthritis. Here, alendronate (ALN) that inhibit osteoclasts was used to study the regulatory effect of osteoclast-derived leukemia inhibitory factor (LIF) on early abnormal bone remodeling. METHODS: This study involved 10-week-old wild-type female C57BL/6 mice and female SOST knockout (KO) mice that were divided into the sham, vehicle, ALN, and SOST KO groups. RESULTS: The expression of LIF was found to decrease by inhibiting osteoclasts, and the histological OA score suggested that the degeneration of articular cartilage was attenuated. Additionally, micro-CT showed that osteoclasts inhibited in the early stage of OA could maintain the microstructure of the subchondral bone. The parameters of bone volume fraction (BV/TV), subchondral bone plate thickness (SBP.Th), and trabecular separation (Tb.Sp) of the treated group were better than those of the vehicle group. CONCLUSIONS: These results suggested that downregulating the expression of sclerostin in osteocytes by secreting LIF from osteoclasts, activate the Wnt/ß-catenin signaling pathway, and promote abnormal bone remodeling in OA. Therefore, clastokine LIF might be a potential molecular target to promote abnormal bone remodeling in early OA.

Extensive cytokine analysis in synovial fluid of osteoarthritis patients.

OBJECTIVE: Osteoarthritis (OA) is a joint disease characterized by articular cartilage loss and afflicts many people worldwide. However, diagnostic methods and treatment options remain limited and are often characterized by low sensitivity and low efficacy. The focus of the present study was to identify proteomic biomarkers in synovial fluid to improve diagnosis and therapy of OA patients. METHODS: Antibody array technology was utilized for protein expression profiling of synovial fluid from 24 OA patients and 24 healthy persons. RESULTS: Compared with healthy persons, twenty proteins showed lower expression levels in OA patients, while thirty proteins had higher levels. Among these differential proteins, GITRL, CEACAM-1, FSH, EG-VEGF, FGF-4, PIGF, Cystatin EM and NT-4 were found for the first time to be differentially expressed in OA. Bioinformatics analysis showed that most of these differential proteins were involved leukocytes events, and some differentially expressed proteins including IL-18, CXCL1, CTLA4, MIP-3b, CD40, MMP-1, THBS1, CCL11, PAI-1, BAFF, aggrecan, angiogenin and follistatin were located in central positions of the protein-protein interaction (PPI) network. CONCLUSION: We speculate that leukocyte proliferation and migration to the joint may be an important pathogenesis of OA, which needs a further validation. The central proteins of the PPI network may play a more pivotal role in OA. The newly identified differentially expressed proteins may be novel biomarkers for OA diagnosis and targets for OA therapy.

ß2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis.

An important causative factor in osteoarthritis (OA) is the abnormal mechanical stress-induced bone remodeling of the subchondral bone. ß2-adrenergic receptor (Adrb2) plays a major role in mechanical stresses that induce bone remodeling. The medial tibial plateau (MTP) and lateral tibial plateau (LTP) of patients with varus Knee osteoarthritis (KO) bear different mechanical stresses. The present study aimed to investigate the expression of Adrb2 in medial tibial plateau subchondral bone (MTPSB) and lateral tibial plateau subchondral bone (LTPSB) in patients with varus KO. A total of 30 tibial plateau samples from patients undergoing total knee arthroplasty for varus KO and MTPSB and LTPSB were studied. Statistical analysis was performed using paired sample t-tests. Safranin O-Fast Green staining and Micro-computed tomography showed significant differences in the bone structure between MTPSB and LTPSB. Tartrate-resistant acid phosphatase (TRAP)-positive cell density in MTPSB was higher than that in LTPSB. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and Western blot analysis revealed that compared to LTPSB, the levels of Adrb2, tyrosine hydroxylase (TH), and osteocalcin increased significantly in MTPSB. Double-labeling immunofluorescence showed Adrb2 was present in the majority of TRAP-positive multinuclear cells of the MTPSB. The expression of Adrb2 and TH was significantly higher in MTPSB than in LTPSB, confirming the involvement of these molecules in the development of OA.

Lycium barbarum polysaccharide protects against osteonecrosis of femoral head via regulating Runx2 expression.

BACKGROUND: Osteonecrosis of femoral head (ONFH) is a pathological state caused by lack of blood supply in femoral head. This study aimed to explore the function of Lycium barbarum polysaccharide (LBP), an antioxidant agent extracted from L. barbarum, on ONFH. METHODS: Osteonecrosis rat model was generated using lipopolysaccharide (LPS) and methylprednisolone followed by examination of body weight, blood glucose, morphology, and BMSC osteoblast differentiation. The effect and underlying mechanism of LBP on the proliferation, apoptosis, and osteoblast differentiation of BMSC were determined with or without LPS or hypoxia treatment using CCK-8. Alizarin Red S staining, flow cytometry, and western blot, respectively. RESULT: LBP could protect against glucocorticoid-induced ONFH in rats, resulting in improved sparse trabecular bone, empty lacunae and bone cell coagulation. Moreover, LBP promoted the proliferation and osteoblast differentiation of bone mesenchymal-derived stem cells (BMSCs) in a dose-dependent manner. Furthermore, LBP enhanced osteoblast differentiation of BMSCs under hypoxia condition. Mechanistically, we found that LBP treatment enhanced Runx2 and ALP expression in BMSCs. LBP restored the expression of Runx2 and ALP under hypoxia, suggesting that LBP might be involved in regulating Runx2/ALP expression and contributed to osteoblast differentiation. Knockdown of Runx2 significantly inhibited BMSCs proliferation, while LBP treatment did not rescue the osteoblast differentiation ability of BMSCs with Runx2 knockdown. CONCLUSION: Our findings suggested that LBP protects against ONFH via regulating Runx2 expression, which could be utilized to treat patients suffering ONFH.

SDF Factor-1α Promotes the Migration, Proliferation, and Osteogenic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells Through the Wnt/ß-Catenin Pathway.

Bone marrow mesenchymal stem cells (BMSCs) are thought to have great potential in the treatment of many diseases and may serve as a cell source for tissue engineering. These cells may be regulated by stromal cell-derived factor-1α (SDF-1α), which has been shown to promote the migration, proliferation, and osteogenic differentiation of BMSCs in inflammation-associated diseases. However, the specific mechanism underlying this process remains unclear. We herein transduced lentivirus carrying SDF-1α, empty vector, or siRNA-SDF-1α into mouse BMSCs and then performed transwell, CCK-8, cell cycle, alkaline phosphatase activity, and Alizarin Red staining experiments on the three groups of samples. Overexpression of SDF-1α promoted the migration, proliferation, and osteogenic differentiation of BMSCs, and SDF-1α upregulated the expression of Wnt pathway-related factors and downstream target genes as determined by western blot, real-time polymerase chain reaction, and immunofluorescence. The effect of low SDF-1α expression on BMSCs was significantly weakened. In addition, we transduced lentivirus carrying siRNA-Wnt3a into BMSCs and treated them with SDF-1 drugs. After inhibiting the Wnt pathway, SDF-1 significantly weakened the migration, proliferation, and osteogenic differentiation of BMSCs. From this, we concluded that high SDF-1 expression can promote the migration, proliferation, and osteogenic differentiation of BMSCs, at least in part by activating the Wnt pathway.

Application of 3D-FS-SPGR imaging combined synovial fluid GGCX detection in the evaluation of knee osteoarthritis.

BACKGROUND: Osteoarthritis represents a kind of chronic and degenerative joint disease characterized by articular cartilage injury and osteoproliferation. Osteoarthritis especially poses a serious threat to the elderly patients. At present, the diagnosis of osteoarthritis mainly consists of clinical examination, X-ray examination, magnetic resonance imaging (MRI), and arthroscopy. However, limitations and misdiagnosis are found within the single method. OBJECTIVES: This article intends to investigate the feasibility of assessing the condition of knee osteoarthritis through quantitative analysis of cartilage using nuclear magnetic resonance 3D fast-spin spoiled gradient-recalled echo (NMR 3D-FS-SPGR) imaging and γ-glutamic acid carboxylase (GGCX) detection in synovial fluid. MATERIAL AND METHODS: A total of 60 patients with primary knee osteoarthritis were enrolled. All the patients were staged and received 3D-FS-SPGR sequence MRI scan for grading based on scan results and cartilage injury. Cartilage tissues were collected for immunohistochemistry (IHC). The GGCX in cartilage was detected using western blotting to analyze the correlation with arthritis. RESULTS: The condition of articular cartilage injury in arthritis patients was clearly observed using 3D-FS-SPGR sequence. The expression of GGCX was decreased in 46 patients (p < 0.05). The expression of GGCX in synovial fluid was significantly reduced following upstaging (p < 0.05). The sensitivity measured using combined 3D-FS-SPGR imaging and synovial fluid GGCX detection for the evaluation of arthritis condition was significantly higher than that of the single detection method (p < 0.05). CONCLUSIONS: Our data showed that the sensitivity of combined detection was obviously higher than single detection for the evaluation of arthritis. The 3D-FS-SPGR combined with synovial fluid GGCX detection could be treated as a promising strategy for arthritis evaluation.

Clinical application of different operative approach of total knee replacement in knee valgus patients. Retrospective cohort study.

PURPOSE: According to the severity of knee valgus, different operative approaches were applied in total knee replacement. Hence, we assessed the safety and efficacy of different operative approaches in the level IV study. METHODS: From May 2011 to March 2014, a retrospectively analysis was conducted among 31 patients with knee valgus (mild in 10 cases, moderate in 8 cases and severe in 13 cases based on Keblish grade). Medial approach trip knee replacement was performed in mild and moderate patients, which were assigned as medial approach group. Lateral approach was performed in severe patients, which was assigned as lateral approach group. Relevant results were compared between medial approach group and lateral approach group, including valgus corrected angle, postoperative knee joint activity and Kss score. Furthermore, operative time, postoperative blood loss, patellar trajectory and anterior knee pain were also compared between the two groups. RESULTS: All operations were successful without obvious complications. In medial approach group, postoperative knee valgus angle was (7 ±â€¯1)°. Three months after operation, degree of knee joint activity was (85.2 ±â€¯5.2)°, and KSS score of knee joint was (80.1 ±â€¯5.2). Significant differences were detected in these compared with preoperative data (all P < .05). Moreover, similar results were found in lateral approach group with postoperative knee valgus angle as (8.2 ±â€¯2.3)°, degree of knee joint activity three months after operation as (85.2 ±â€¯5.3)°, and KSS score of knee joint as (80.3 ±â€¯3.2). However, no significant differences were found among these three groups in operative time, postoperative blood loss, patellar trajectory or anterior knee pain. CONCLUSIONS: Different operative approaches in total knee replacement according to the severity of knee valgus were proved as effective and safe procedures, which deserved further application.