Erratum: ATR inhibition sensitizes liposarcoma to doxorubicin by increasing DNA damage.

[This corrects the article on p. 1577 in vol. 12, PMID: 35530299.].

ATR inhibition sensitizes liposarcoma to doxorubicin by increasing DNA damage.

Liposarcomas account for approximately 20% of all adult sarcomas and have limited therapeutic options outside of surgery. Inhibition of ataxia-telangiectasia and Rad3 related protein kinase (ATR) has emerged as a promising chemotherapeutic strategy in various cancers. However, its activation, expression, and function in liposarcoma remain unkown. In this study, we investigated the expression, function, and potential of ATR as a therapeutic target in liposarcoma. Activation and expression of ATR in liposarcoma was analyzed by immunohistochemistry, which was further explored for correlation with patient clinical characteristics. ATR-specific siRNA and the ATR inhibitor VE-822 were applied to determine the effect of ATR inhibition on liposarcoma cell proliferation and anti-apoptotic activity. Migration activity and clonogenicity were examined using wound healing and clonogenic assays. ATR (p-ATR) was overexpressed in 88.1% of the liposarcoma specimens and correlated with shorter overall survival in patients. Knockdown of ATR via specific siRNA or inhibition with VE-822 suppressed liposarcoma cell growth, proliferation, migration, colony-forming ability, and spheroid growth. Importantly, ATR inhibition significantly and synergistically enhanced liposarcoma cell line chemosensitivity to doxorubicin. Our findings support ATR as critical to liposarcoma proliferation and doxorubicin resistance. Therefore, the addition of ATR inhibition to a standard doxorubicin regimen is a potential treatment strategy for liposarcoma.

Expression and Clinical Significance of High-Mobility Group AT-hook 2 (HMGA2) in Osteosarcoma.

OBJECTIVE: Although high-mobility group AT-hook 2 (HMGA2) has been shown to have crucial roles in the pathogenesis and metastasis of various malignancies, its expression and significance in osteosarcoma remain unknown. Here we evaluate the expression, clinical prognostic value, and overall function of HMGA2 in osteosarcoma. METHODS: Sixty-nine osteosarcoma patient specimens within a tissue microarray (TMA) were analyzed by immunohistochemistry for HMGA2 expression. Demographics and clinicopathological information including age, gender, tumor location, metastasis, recurrence, chemotherapy response, follow-up time, and disease status were also collected. After validation of expression, we determined whether there was a correlation between HMGA2 expression and patient clinicopathology. HMGA2 expression was also evaluated in osteosarcoma cell lines and patient tissues by Western blot, we analyzed the expression of HMGA2 in the human osteosarcoma cell lines MG63, 143B, U2OS, Saos-2, MNNG/HOS, and KHOS. HMGA2-specific siRNA and clonogenic assays were then used to determine the effect of HMGA2 inhibition on osteosarcoma cell proliferation, growth, and chemosensitivity. RESULTS: HMGA2 expression was elevated in the osteosarcoma patient specimens and human osteosarcoma cell lines. HMGA2 was differentially expressed in human osteosarcoma cell lines. Specifically, a relatively high expression of HMGA2 was present in KHOS, MNNG/HOS, 143B and a relatively low expression was in MG63, U2OS as well as Saos-2. HMGA2 expression is correlated with metastasis and shorter overall survival. High HMGA2 expression is an independent predictor of poor osteosarcoma prognosis. There was no significant correlation between HMGA2 expression and the age, gender, or tumor site of the patient. HMGA2 expression is predominantly within the nucleus. The expression of HMGA2 also directly correlated to neoadjuvant chemoresistance. There was a significant reduction of HMGA2 expression in the siRNA transfection group. After the use of siRNA, the proliferation of osteosarcoma cells is decreased and the chemosensitivity of osteosarcoma cells is significantly increased. CONCLUSION: Our study supports HMGA2 as a potential prognostic biomarker and therapeutic target in osteosarcoma.

The Role of Zinc in Bone Mesenchymal Stem Cell Differentiation.

Zinc is an essential trace element for bone growth and bone homeostasis in the human body. Bone mesenchymal stem cells (BMSCs) are multipotent progenitors existing in the bone marrow stroma with the capability of differentiating along multiple lineage pathways. Zinc plays a paramount role in BMSCs, which can be spurred differentiating into osteoblasts, chondrocytes, or adipocytes, and modulates the formation and activity of osteoclasts. The expression of related genes also changed during the differentiation of various cell phenotypes. Based on the important role of zinc in BMSC differentiation, using zinc as a therapeutic approach for bone remodeling will be a promising method. This review explores the role of zinc ion in the differentiation of BMSCs into various cell phenotypes and outlines the existing research on their molecular mechanism.

Increased EHHADH Expression Predicting Poor Survival of Osteosarcoma by Integrating Weighted Gene Coexpression Network Analysis and Experimental Validation.

Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), a member of the 3-hydroxyacyl-CoA dehydrogenase family, were previously demonstrated to be involved in the tumorigenesis of various cancer types. This study is aimed at determining of the diagnostic and prognostic value of EHHADH in osteosarcoma (OS). The overexpression of EHHADH was found both in OS and also other sarcoma types, and according to the retrospective cohort study, the EHHADH level was related to the overall survival and disease-free survival of the OS patients. Furthermore, knockdown of EHHADH under the influence of EHHADH small interfering RNA significantly suppressed the proliferation ability of the tumor cells. Moreover, EHHADH overexpressed was found in human OS tissues. In summary, the progression of OS could be enhanced by EHHADH, which may be a potential diagnostic and prognostic biomarker for OS patients.

Efficacy of Arthroscopic Treatment for Concurrent Medial Meniscus Posterior Horn and Lateral Meniscus Anterior Horn Injury: A Retrospective Single Center Study.

OBJECTIVE: To investigate the effectiveness of arthroscopic surgery for combined tears of the posterior horn of the medial meniscus (PHMM) and the anterior horn of the lateral meniscus (AHLM). METHODS: Between September 2009 and December 2013, a retrospective investigation was performed on 48 patients (48 knees) with combined tears of PHMM and AHLM who underwent arthroscopic surgery. All patients underwent magnetic resonance imaging (MRI) diagnosis in the outpatient department. After admission, other basic examinations were performed. PHMM was treated with partial meniscectomy and AHLM was treated with external-internal suture or partial meniscectomy. Curative effect was evaluated according to Lysholm score and IKDC score. The differences of the functions as well as Lysholm and IKDC scores pre- and postoperatively were compared, while the diagnostic accuracy of MRI and arthroscopy for PHMM and AHLM were compared. RESULTS: Seven patients with combined tears of PHMM and AHLM were misdiagnosed during MRI examination when arthroscopy was used as the gold standard. All patients were followed up for an average of 34.58 months (range 10-52 months) and all incisions healed by first intention with no obvious complication. The preoperative and postoperative Lysholm scores were 47.22 ± 2.77 and 87.36 ± 5.45, respectively. The IKDC scores are 54.73 ± 4.65 preoperatively and 89.62 ± 3.71 postoperatively. The positive rates of the diagnosis through MRI and arthroscopic surgery is 85.42% and 100%, respectively. At the last follow-up, the patients had no pain, weakness, and instability, and tenderness in medial and lateral joint space disappeared. Mcmurray test was weakly positive in four patients. Excellent outcome was achieved in 39 cases, and a good outcome was achieved in five cases; the good to excellent rate was 91.67%. CONCLUSION: MRI examination of combined tears of PHMM and AHLM may result in misdiagnosis. Arthroscopic primary repair seemed to be an effective surgical option for treatment of combined tears of PHMM and AHLM.

Expression and clinical implications of leucine-rich repeat containing 15 (LRRC15) in osteosarcoma.

Leucine-rich repeat containing 15 (LRRC15) is a member of the leucine-rich repeat superfamily that is overexpressed in various cancers and associated with higher tumor grade and aggression. Despite its known tumorigenicity, its roles within osteosarcoma are unknown, prompting us to evaluate its expression and clinical significance within this rare yet aggressive cancer. Western blots showed differential expression of LRRC15 in the osteosarcoma cell lines MNNG/HOS, KHOS, 143B, MG63, Saos-2, and U2OS. We additionally validated this positive expression, as well as sublocalization to the cell membrane, with immunofluorescence. A tissue microarray constructed from 69 osteosarcoma patient tissues was immunohistochemically stained for LRRC15 expression, stratified, and used for clinicopathological analysis. Publicly available databases on LRRC15 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2) were also analyzed. We found 63 of the 69 (91.3%) patient tissues exhibited some degree of LRRC15 immunostaining, including no staining (6 of 69, 8.7%), 1+ staining (12 of 69, 17.4%), 2+ staining (25 of 69, 36.2%), and 3+ staining (26 of 69, 37.7%). The patients with osteosarcomas having elevated LRRC15 expression demonstrated comparatively increased metastasis, chemoresistance, and shorter 5-year survival rates. Our analysis of the TARGET-OS and GENT2 databases also showed increased LRRC15 gene expression in osteosarcoma. Taken together, our study supports LRRC15 as a prognostic biomarker and emerging therapeutic target in osteosarcoma.

The role of extracelluar matrix in osteosarcoma progression and metastasis.

Osteosarcoma (OS) is the most common primary bone malignancy and responsible for considerable morbidity and mortality due to its high rates of pulmonary metastasis. Although neoadjuvant chemotherapy has improved 5-year survival rates for patients with localized OS from 20% to over 65%, outcomes for those with metastasis remain dismal. In addition, therapeutic regimens have not significantly improved patient outcomes over the past four decades, and metastases remains a primary cause of death and obstacle in curative therapy. These limitations in care have given rise to numerous works focused on mechanisms and novel targets of OS pathogenesis, including tumor niche factors. OS is notable for its hallmark production of rich extracellular matrix (ECM) of osteoid that goes beyond simple physiological growth support. The aberrant signaling and structural components of the ECM are rich promoters of OS development, and very recent works have shown the specific pathogenic phenotypes induced by these macromolecules. Here we summarize the current developments outlining how the ECM contributes to OS progression and metastasis with supporting mechanisms. We also illustrate the potential of tumorigenic ECM elements as prognostic biomarkers and therapeutic targets in the evolving clinical management of OS.

TLRs Play Crucial Roles in Regulating RA Synoviocyte.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease comparing the inflammation of synovium. Macrophage-like synoviocytes and fibroblast-like synoviocytes (synoviocytes) are crucial ingredients of synovium. Therein, a lot of research has focused on synoviocytes. Researches demonstrated that TLR1, TLR2, TLR3, TLR4, TLR5, TLR6 TLR7 and TLR9 are expressed in synoviocyte. Additionally, the expression of TLR2, TLR3, TLR4 and TLR5 is increased in RA synoviocyte. In this paper, we review the exact role of TLR2, TLR3, TLR4 and TLR5 participate in regulating the production of inflammatory factors in RA synoviocyte. Furthermore, we discuss the role of vasoactive intestinal peptide (VIP), MicroRNA, Monome of Chinese herb and other cells (Monocyte and T cell) influence the function of synoviocyte by regulating TLRs. The activation of toll-like receptors (TLRs) in synoviocyte leads to the aggravation of arthritis, comparing with angiogenesis and bone destruction. Above all, TLRs are promising targets for managing RA.

Biomechanical study of medial meniscus after posterior horn injury: a finite element analysis.

We established an effective finite element model of knee joint for observation of stress and displacement of meniscus related changes after medial meniscus injury. Different types of medial meniscus injury can lead to varied meniscus stress and displacement changes. Stress and displacement concentration were found in fissure tip of meniscus tear compared to normal meniscus. The posterior horn injury of medial meniscus may initiate combined injury of medial meniscus posterior horn (MMPH) and that of medial meniscus body, and combined injury of MMPH and that of lateral meniscus anterior horn; fissure expansions regarding horizontal fissure, longitudinal fissure and grip-shaped fissure of MMPH were spotted.

Application of Self-Made Connection Device in Intractable Intramedullary Device.

BACKGROUND: Intramedullary fixation a standard surgical technique for long bone meta/diaphyseal fractures. There were many difficulties in removal of the intractable intramedullary device. The authors reported a new technique to remove the intractable intramedullary nail by using a self-made connecting device. METHODS: The subject underwent removal of the intramedullary nail using a self-made connecting device, the core components of which were a caudal connecting rod and a sliding hammer in the common intramedullary nail removal device, and the auxiliary device was mainly a clinically commonly used Kirschner wire (K-wire; diameter 1.5-2.5 mm). In technical procedure, the key point was the connection between the k-wire and the intramedullary device, according to the specific conditions of the intramedullary device. RESULTS: From 2012 to 2017, a total of 10 cases of intractable intramedullary devices were taken out using this self-made connection device, including 7 cases of tibial intramedullary nails, 1 case of femoral nail, and 1 case of tibial elastic nail. The technique provided satisfactory results, no infection or re-fracture occurred after the. CONCLUSION: The self-made connecting device may provide new technique for more surgeons in the face of intractable intramedullary device.

Expression of TGF-ß1 and VEGF in patients with Achilles tendon rupture and the clinical efficacy.

Expression of transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) in patients with Achilles tendon rupture, and the predictive values and significance in clinical efficacy were explored. Forty-two patients with Achilles tendon rupture, surgically treated in the First Affiliated Hospital of University of South China, were selected and the clinical efficacy was evaluated based on the American Orthopaedic Foot and Ankle Society (AOFAS) scoring system. RT-qPCR was adopted to detect the expression of serum TGF-ß1 and VEGF in the patients before and after treatment, and Spearman's correlation was used to analyze the correlation of TGF-ß1 and VEGF with the clinical efficacy after treatment. Patients were divided into an excellent efficacy group and a good/general efficacy group according to the predictive efficacy. In the two groups, the expression levels of TGF-ß1 and VEGF before treatment were observed, and the predictive values of TGF-ß1 and VEGF in clinical efficacy using the receiver operating characteristic (ROC) curves were obtained. The 42 patients showed significantly higher expression of TGF-ß1 and VEGF at 3 months after treatment, and significantly decreased expression at 6 months after treatment, compared to the results before treatment (both P<0.001). After treatment, the efficacy was excellent in 11 patients, good in 25 and general in 6. Spearman's correlation analysis revealed that the expression of TGF-ß1 and VEGF decreased with the improvement of efficacy after treatment (P<0.001), and the excellent efficacy group showed significantly lower expression of TGF-ß1 and VEGF than that in the good/general efficacy group (P<0.01). Moreover, according to ROC curves, the areas under the curves (AUCs) of TGF-ß1 and VEGF were 0.651 and 0.645, respectively. In conclusion, TGF-ß1 and VEGF can be considered as observational indexes and predictors for clinical efficacy in patients with Achilles tendon rupture, before and after treatment.

Comparison of arthroscopic versus open surgery on external snapping hip caused by gluteal muscle contracture.

PURPOSE: To compare the outcomes of contracture release by arthroscopic versus open surgical approach in patients with external snapping hip (ESH) caused by gluteal muscle contracture (GMC). METHODS: Medical records of patients with ESH due to GMC who underwent open surgery (n = 44) or arthroscopic surgery (n = 48) between October 2008 and October 2014 were reviewed. Patients were followed up at 1, 3, 12, and 24 months postoperatively. Operation time, incision length, postoperative pain, postoperative complication rate, and recurrence rate were compared between the 2 groups. Hip adduction, and Harris Hip Scores (HHS) at 1 and 2 years postoperatively were compared between the groups and with preoperative data. RESULTS: Mean operation time did not differ between the 2 groups (p>0.05). The arthroscopic surgery group had smaller incisions (p<0.05), less postoperative pain (p<0.05), lower complication rates (p<0.05) than did the open surgery group. The recurrence rates were similar for the 2 groups (p>0.05). Hip adduction, and HHS 1 year and 2 years postoperatively were significantly better postoperatively than they had been preoperatively for both groups (all p<0.01), and were similar for the 2 groups (all p>0.05). CONCLUSIONS: Arthroscopic release of contracture tissue is a safe and effective approach for the treatment of ESH caused by GMC, with the advantages of small scars, less postoperative pain, fewer complications compared with open surgery.

Arthroscopic Repair of Chronic Tears of the Anterior Horn of the Lateral Meniscus That Includes Covering the Lesion With an Infrapatellar Pedicle Fat Flap.

This study analyzed the efficacy and safety of arthroscopic outside-in repair of the anterior horn of the lateral meniscus that includes covering the lesion with an infrapatellar pedicle fat flap in patients with chronic tears. This retrospective study reviewed 87 patients with chronic tears of the anterior horn of the lateral meniscus who underwent arthroscopic outside-in repair, which included covering the lesion with an infrapatellar pedicle fat flap (group A, n=45) or not (group B, n=42). The 2 groups were similar in terms of age, sex, body mass index, and disease duration. Patient results were assessed with Tegner, Lysholm, and visual analog scale scores; healing criteria; magnetic resonance imaging; and complication rates. Mean follow-up was 38.2 months. Tegner and Lysholm scores improved postoperatively in both groups (all P<.01) and were similar for the 2 groups (all P>.05). Visual analog scale scores were reduced postoperatively in both groups (P<.01) and similar for the 2 groups (P>.05). Healing rates and complication rates did not differ between the 2 groups (all P>.05), but healing on magnetic resonance imaging was better in group A than group B (P<.05). The repair of chronic tears of the anterior horn of the lateral meniscus can lead to good clinical outcomes and a satisfactory success rate. Covering the repair site with an infrapatellar pedicle fat flap may improve meniscal healing and does not increase the complication rate. [Orthopedics. 2018; 41(3):e360-e364.].

Comparison of arthroscopic versus open surgery on external snapping hip caused by gluteal muscle contracture.

PURPOSE: To compare the outcomes of contracture release by arthroscopic versus open surgical approach in patients with external snapping hip (ESH) caused by gluteal muscle contracture (GMC). METHODS: Medical records of patients with ESH due to GMC who underwent open surgery (n = 44) or arthroscopic surgery (n = 48) between October 2008 and October 2014 were reviewed. Patients were followed up at 1, 3, 12, and 24 months postoperatively. Operation time, incision length, postoperative pain, postoperative complication rate, and recurrence rate were compared between the 2 groups. Hip adduction, and Harris Hip Scores (HHS) at 1 and 2 years postoperatively were compared between the groups and with preoperative data. RESULTS: Mean operation time did not differ between the 2 groups (p>0.05). The arthroscopic surgery group had smaller incisions (p<0.05), less postoperative pain (p<0.05), lower complication rates (p<0.05) than did the open surgery group. The recurrence rates were similar for the 2 groups (p>0.05). Hip adduction, and HHS 1 year and 2 years postoperatively were significantly better postoperatively than they had been preoperatively for both groups (all p<0.01), and were similar for the 2 groups (all p>0.05). CONCLUSIONS: Arthroscopic release of contracture tissue is a safe and effective approach for the treatment of ESH caused by GMC, with the advantages of small scars, less postoperative pain, fewer complications compared with open surgery.

[DIAGNOSIS AND TREATMENT OF ACETABULAR LABRUM INJURY IN PIPKIN FRACTURE].

OBJECTIVE: To observe the characteristics of acetabular labrum injury in Pipkin fractures and the effectiveness of repairing the labrum with suture anchor. METHODS: Between July 2010 and July 2013, 10 cases of Pipkin fractures accompanied by acetabular labrum injury were treated. There were 7 males and 3 females with an average age of 32.5 years (range, 24-56 years). The causes of injury included traffic accident in 8 cases and falling from height in 2 cases. According to the Pipkin classification criteria, there were 6 cases of type II, 2 cases of type III, and 2 cases of type IV. The average interval from injury to operation was 8 days (range, 6-14 days). All the patients underwent open reduction and internal fixation through transtrochanteric approach with trochanteric osteotomy, and repair the labrum with suture anchor. The effectiveness was evaluated according to the Thompson & Epstein scoring scales after operation. RESULTS: All incisions healed primarily without early complication of deep infection or deep vein thrombosis of lower limb. All the cases were followed up 22 months on average (range, 12-48 months). X-ray films showed that all osteotomies and acetabular fractures healed within 3-4 months, femoral head and femoral neck fracture healed within 6-11 months. MRI examinations showed that all repaired acetabular labrums well healed. One case had necrosis of the femoral head at 12 months after operation, and was treated by total hip arthroplasty. According to the Thompson & Epstein scoring scales at last follow-up, the results were excellent in 5 cases, good in 3 cases, fair in 1 case and poor in 1 case, with an excellent and good rate of 80%. CONCLUSION: The diagnosis of acetabular labrum injury can be easily missed during Pipkin fracture, preoperative diagnosis should be combined with hip MRI. Trochanteric osteotomy through transtrochanteric approach , and repairing the labrum with suture anchor can restore the hip function effectively.

A systematic review and adjusted indirect comparison of oral anticoagulants.

EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Recognize the high risk of postoperative venous thromboembolism (VTE) in patients undergoing major orthopedic surgery. 2. Distinguish the different pharmacological mechanisms of VTE prophylaxis drugs. 3. Delineate the advantages and disadvantages of each VTE prophylaxis drug. 4. Recognize that rivaroxaban is as efficacious as apixaban but can increase the risk of hemorrhage. Patients undergoing major orthopedic surgery are at high risk for developing postoperative venous thromboembolism (VTE). The authors analyzed the available evidence on the efficacy and safety of dabigatran, apixaban, and rivaroxaban vs low-molecular-weight heparins (LMWHs) as VTE prophylaxis in major orthopedic surgery. Outcomes evaluated included total VTE, deep venous thrombosis (DVT), pulmonary embolism (PE), death, and major bleeding. Rivaroxaban and apixaban are more efficacious than dabigatran and are as safe as dabigatran. Rivaroxaban is as efficacious as apixaban but can increase the risk of hemorrhage.

The emerging role of circulating microRNAs as biomarkers in autoimmune diseases.

The highly conserved RNAs known as microRNAs (miRNAs) are a class of small, single-stranded, non-coding RNAs that play a critical role in the regulation of host genome expression at the posttranscriptional level. MiRNA-mediated gene regulation is vital for normal cellular functions, such as the cell differentiation, proliferation and apoptosis, and nearly one-third of human messenger RNAs might be miRNA targets. Increasing evidence has suggested that miRNAs play a critical role in the regulating the immune system and preventing autoimmune disorders. Circulating miRNAs, which can be easily detected by a non-invasive methods, have been proven to be able to distinguish diseased individuals from healthy subjects. In addition, these circulating miRNAs have relatively high sensitivity and specificity and thus have been developed as biomarkers for the diagnosis and monitoring of human diseases. To date, nearly 100 circulating miRNAs have been proven to be biomarkers for various diseases, and this number continues to rise. This review aims to summarize the most promising identified circulating miRNAs as potential biomarkers in autoimmune diseases and to discuss current challenges and future directions in the field.

A polysaccharide from Agaricus blazei inhibits proliferation and promotes apoptosis of osteosarcoma cells.

Many reports have proved that traditional Chinese herbal medicines (TCM) have become popular used in disease prevention and as alternatives to cancer chemotherapy. In this study, we purified a polysaccharide (ABP-Ia) from the fruiting bodies of Agaricus blazei and identified its molecular weight to be 4.2×10(5)Da. ABP-Ia was a heteropolysaccharide fraction consisting of glucose, mannose, and galactose in a molar ratio of 1:1:1, along with trace of rhamnose. The effect of ABP-Ia at three concentrations of 100, 200 and 400 µg/mL on the cell growth and apoptosis was evaluated in osteosarcoma cell lines HOS and a normal human osteoblast cell line NHOst. ABP-Ia had a significant inhibitory effect against the growth of HOS cells, whereas a mild cytotoxicity to the HOS cells mediated by ABP-Ia was observed, which was in accordance with the results that ABP-Ia substantially induced apoptosis in a dose-dependent fashion in the HOS cells. However ABP-Ia had no or minor inhibitory and cytotoxic effects on the viability of NHOst cells even at the high concentration of 400 µg/mL. Base on all the observations, we could conclude that ABP-Ia had an evident inhibitory effect on the growth of HOS cells mainly through induction of apoptosis, with a minor toxicity to normal human osteoblast cell.

Epigenetic changes in osteosarcoma.

Osteosarcoma is one of the most prevalent primary bone tumors. The pathogenesis and molecular development of this tumor remains elusive. The prognosis is unfavorable due to lack of effective treatment methods. Recent advances in the epigenetics have brought a profound impact on the understanding of molecular mechanisms that lead to osteosarcoma. In this review, we summarized the current literature on epigenetic changes that are thought to contribute to the carcinogenesis of osteosarcoma, and discussed the potential diagnostic and therapeutic applications as well as future areas of research.