Erratum: Long non-coding RNA HOTAIRM1-1 silencing in cartilage tissue induces osteoarthritis through microRNA-125b.

[This corrects the article DOI: 10.3892/etm.2021.10365.].

The Roles of KIFC1 in the Development of Osteosarcoma: Characterization of Potential Therapeutic Targets.

Background: As an important member of the mitotic kinesin family, kinesin family member C1 (KIFC1) is abnormally expressed in a variety of tumors. However, the roles of KIFC1 in the development of osteosarcoma (OS) have never been elucidated. Methods: The expression of KIFC1 in OS tissues which was detected by immunohistochemistry (IHC) staining was further confirmed by Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. The relationship between KIFC1 and CDC20 was analyzed by clinical data, STRING database, and GEPIA2 database. Survival analysis was performed through GEPIA2 database. To elucidate the roles of KIFC1 in OS, MG-63 and U-2 OS cells were treated with short hairpin RNA (shRNA) to knock down KIFC1 expression, and the knockdown efficiency was validated with quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB). Moreover, colony formation and Cell Counting Kit-8 (CCK-8) assays were utilized to evaluate cell proliferation. Results: According to IHC staining and GEPIA2 analysis, the expression of KIFC1 in OS tissues was significantly higher than that in adjacent normal tissues, which was inversely connected to the prognosis. These results were consistent with our clinical data. Besides, KIFC1 was positively correlated with CDC20. In addition, KIFC1 shRNA could effectively silence KIFC1 expression in MG-63 and U-2 OS cells. Furthermore, the knockdown of KIFC1 inhibited the cell proliferation ability with increased cell apoptosis in MG-63 and U-2 OS cells. Conclusion: KIFC1 was significantly upregulated in OS and promoted OS progression by cell proliferation. These findings offered new clues for OS diagnosis and prognosis, suggesting KIFC1 could be a potential therapeutic target for OS in further study.

Long non-coding RNA HOTAIRM1-1 silencing in cartilage tissue induces osteoarthritis through microRNA-125b.

Aberrations in long noncoding RNA (lncRNA) expression have been recognized in numerous human diseases. In the present study, the of role the long noncoding RNA HOX antisense intergenic RNA myeloid 1 variant (HOTAIRM1-1) in regulating the pathological progression of osteoarthritis (OA) was investigated. The aberrant expression of HOTAIRM1-1 in OA was demonstrated, but the molecular mechanisms require further analysis. The aim of the present study was to explore the function of miR-125b in modulating chondrocyte viability and apoptosis, and to address the functional association between HOTAIRM1-1 and miR-125b as potential targets. A miR-125b inhibitor was used, which laid the foundation for the following investigation. The study confirmed that HOTAIRM1-1 and miR-125b are inversely expressed in chondrocytes. The expression of HOTAIRM1-1 was downregulated and the expression of miR-125b was upregulated in tissues from patients with OA. HOTAIRM1-1 directly interacted with miR-125b in chondrocytes. HOTAIRM1-1 knockdown was associated with chondrocyte proliferation and extracellular matrix degradation. Furthermore, miR-125b reversed the effect of HOTAIRM1-1 on cell proliferation and apoptosis. In conclusion, the present study indicates that the loss of HOTAIRM1-1 function leads to aberrant increases in the proliferation and apoptosis of chondrocytes. miR-125b may be a potential downstream mechanism that regulates the function of HOTAIRM1-1, and this finding provides a therapeutic strategy for OA.

Three-Portal Approach of Arthroscopy for Anterior Ankle Impingement Syndrome: A Propensity Score-Matched Analysis.

OBJECTIVE: To introduce a 3-portal approach of arthroscopic for anterior ankle impingement syndrome and to compare this method with 2-portal arthroscopy. METHODS: From July 2011 to April 2019, a total of 52 patients (30 females, 22 males) with anterior ankle impingement syndrome underwent surgery with 2-portal approach (anterior medial and anterior lateral approach; N = 26) and modified 3-portal approach (anterior medial, anterior lateral, and an accessory anterior median approach; N = 26) of arthroscopic were recruited retrospectively after we performed a propensity score-matched analysis (PSMA). The mean age at operation time was 44.1 years (range from 22 years to 74 years) and the mean follow-up duration was more than two years (range from 2 years to 9 years). Clinical outcomes of all patients were evaluated according to the range of motion (ROM, dorsal flex angle), the American Orthopaedic Foot and Ankle Society lesser metatarsophalangeal interphalangeal scale (AOFAS), the visual analogue scale (VAS), and the operation time before and after the surgery. RESULTS: During the follow-up period, both two groups indicated significant improvement in these function scores. Clinical assessment showed that for the 2-portal approach of arthroscopic the total average of AOFAS scores were significantly increased from preoperative 59.91 ± 5.281 points to postoperative 76.18 ± 1.471 points (P = 0.02), the VAS scores were significantly decreased from preoperative 7.64 ± 0.924 points to postoperative 4.18 ± 0.982 points (P = 0.04), and the dorsal flex angle was significantly increased from preoperative 12.27° ± 6.467° to postoperative 21.36° ± 3.931° at the last follow-up (P = 0.035). However, for the 3-portal approach of arthroscopic the total average of AOFAS scores were significantly increased from preoperative 48.64 ± 9.646 points to postoperative 79.18 ± 6.555 points (P = 0.015), the VAS scores were significantly decreased from preoperative 7.82 ± 0.751 points to postoperative 2.64 ± 1.629 points (P = 0.01), and the dorsal flex angle was significantly increased from preoperative 13.64° ± 7.775° to postoperative 20.45° ± 6.502° at the last follow-up (P = 0.045). There were no significant differences among the dorsal flex angle, the AOFAS scores, and the VAS scores between the two groups at the last follow-up (P > 0.05). Although the operation time of the 3-portal approach of arthroscopic (74.82 ± 18.395 min) was longer than that of the 2-portal approach of arthroscopic (92.55 ± 27.153 min), the difference was not significant (P > 0.05). CONCLUSION: Both the 2-portal and the 3-portal approach of arthroscopic provides almost the same satisfactory clinical outcomes for anterior ankle impingement syndrome, but we strongly suggest the 3-portal approach of arthroscopic which can supply greater joint contact area to treat advanced impingement syndrome for a good result.

miR-155-5p regulates macrophage M1 polarization and apoptosis in the synovial fluid of patients with knee osteoarthritis.

Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases that affects millions of individuals worldwide. During OA, proinflammatory factors (including IL-1, IL-6, IL-17 and TNF-α) are released from chondrocytes and proliferating synoviocytes potentiate the proinflammatory microenvironment of the synovial fluid (SF). The altered SF microenvironment affects the infiltration, polarization and apoptosis of macrophages, though the underlying mechanisms are not completely understood. In the present study, the hypothesis that the knee synovial fluid of patients with knee osteoarthritis (KOA SF) promotes the polarization of peripheral blood mononuclear cell (PBMC)-derived M1 macrophages and inhibits PBMC-derived macrophage apoptosis was investigated. KOA SF increased PBMC-derived macrophage M1 polarization via the microRNA (miR)-155-5p/suppressor of cytokine signaling 1 signaling pathway. Caspase-3 (CASP3) was identified as a novel target of miR-155-5p, where KOA SF inhibited macrophage apoptosis via the miR-155-5p/CASP3 signaling pathway. The results suggested that the proinflammatory environment of KOA SF promoted macrophage M1 polarization and reduced macrophage apoptosis via miR-155-5p. The results provided a potential explanation for the increased number of M1 macrophages observed in KOA SF during OA. In addition, the present study suggested that miR-155-5p may serve as a potential therapeutic target for KOA.

Identification of Abnormal Spindle Microtubule Assembly as a Promising Therapeutic Target for Osteosarcoma.

OBJECTIVE: To demonstrate the expression of abnormal spindle microtubule assembly (ASPM) in clinical osteosarcoma tissue specimens collected in our hospital, and to explore the function of ASPM in osteosarcoma in vitro and in vivo. METHODS: Tissue specimens from 82 cases of osteosarcoma were collected and analyzed by immunohistochemistry assay. We also investigated the relationship between ASPM expression and clinicopathological characteristics in the patients. We transfected shASPM plasmid and the empty control plasmid, respectively, and then used quantitative polymerase chain reaction and western blot analysis to detect ASPM expression. Cell colony assay and MTT were used to observe the proliferation ability. In vivo study was undertaken to explore the ASPM function further. RESULTS: In this study, ASPM showed high expression in osteosarcoma tissue samples compared with non-tumor normal tissues. ASPM was positively correlated with clinical pathological characteristics, including tumor size (P = 0.024) and clinical stage (P = 0.045). Our results further showed that ASPM depletion dramatically inhibited the proliferation of osteosarcoma cells (with fewer cells in the sh-RNA-ASPM group compared with the control group(P < 0.05, respectively), and the in vivo assays further confirmed that ASPM ablation markedly blocked tumor growth compared with control (P < 0.05). CONCLUSION: Our data provides strong evidence that the high expression of ASPM in osteosarcoma promotes proliferation in vitro and in vivo, indicating its potential role as an osteosarcoma therapeutic target.

Comparison between epsilon-aminocaproic acid and tranexamic acid for total hip and knee arthroplasty: A meta-analysis.

BACKGROUND: The aim was to compare the efficacy and safety of epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Potential academic articles were identified from the Cochrane Library, Springer, PubMed, and ScienceDirect databases from inception to December 2019. Randomized controlled trials (RCTs) and non-RCTs involving EACA and TXA in THA or TKA were included. Pooled data were analyzed using RevMan 5.1. RESULTS: Three RCTs and three non-RCTs met the inclusion criteria. The present meta-analysis reveals that EACA is associated with significantly more blood loss than TXA. No significant differences were identified in terms of blood transfusion rate, transfusion units, hemoglobin (Hb) level at discharge, operation time, length of hospital stay, deep venous thrombosis (DVT), or 30-day readmission. CONCLUSIONS: Compared with TXA, EACA led to more blood loss in patients undergoing THA or TKA. However, there was no significant difference in the blood transfusion rate, transfusion units, Hb level at discharge, operation time, length of hospital stay, DVT, or 30-day readmission between groups.

Identification of Lysosome-Associated Protein Transmembrane-4 as a Novel Therapeutic Target for Osteosarcoma Treatment.

OBJECTIVE: The aim of the study is to evaluate the expression of lysosome-associated protein transmembrane-4 (LAPTM4B) in human osteosarcoma tissue samples collected in our hospital, and to explore the possible correlations between the clinical pathological features of osteosarcoma patients and LAPTM4B expression. METHODS: Immunohistochemical (IHC) assays were performed to detect the expression levels of LAPTM4B in 62 tissue samples of osteosarcoma tissues and corresponding non-tumor tissues. According to LAPTM4B staining intensity in tumor tissues, osteosarcoma patients were classified into LAPTM4B high expression and low expression groups. In addition, the potential correlations between LAPTM4B expression levels and clinical pathological features were evaluated. In addition, we detected the effects of LAPTM4B on the proliferation and invasion of esteosarcoma cells through colony formation assay and transwell assay, respectively. We further explored the potential effects of LAPTM4B on tumor growth and metastasis using in vivo animal model. RESULTS: We revealed that LAPTM4B was highly expressed in human osteosarcoma tissues. We determined the significance between LAPTM4B and clinical features, including the tumor size (P = 0.004*) and the clinical stage (P = 0.035*) of osteosarcoma patients. Our results further demonstrated that ablation of LAPTM4B obviously blocked the proliferation and invasion of osteosarcoma cells in vitro and restrained tumor growth and metastasis in mice. CONCLUSION: We investigated the potential involvement of LAPTM4B in osteosarcoma progression and confirmed LAPTM4B as a novel therapeutic target for osteosarcoma.

The role of fibroblast activation protein in progression and development of osteosarcoma cells.

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

APLNR promotes the progression of osteosarcoma by stimulating cell proliferation and invasion.

Osteosarcoma is the most common type of bone malignancies with a poor prognosis. In recent years, targeted therapy has shown great potential in the treatment of osteosarcoma, and more effective therapeutic targets for this disease need to be developed. APLNR is a seven transmembrane G-protein-coupled receptor expressed widely in multiple tissues. As has been reported, APLNR is involved in various physiological and pathological processes. Although APLNR plays a role in the development and progression of multiple tumors, the potential role of APLNR in osteosarcoma, a highly malignant tumor, remains unclear. Here, we reported that APLNR expression was correlated positively with clinical features including tumor size and stage of osteosarcoma. We found that APLNR knockdown inhibited the proliferation and invasion of osteosarcoma cells in vitro. In addition, APLNR could promote the progression and metastasis of osteosarcoma in mice. Collectively, this study showed the potential link between APLNR and osteosarcoma and suggested APLNR as a novel therapeutic target for osteosarcoma.