lncRNA HCG11 suppresses human osteosarcoma growth through upregulating p27 Kip1.

Osteosarcoma (OS) is a common malignant bone cancer threatening children and young adults. Emerging evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in the progression of OS. Herein, we want to clarify the roles of lncRNA human leukocyte antigen complex group 11 (HCG11) in OS. Our data revealed that HCG11 expression is decreased in OS, which is a result of transcriptional repression of YY1. Low HCG11 level is closely associated with larger tumor size and shorter overall survival of OS patients. HCG11 negatively regulates cell proliferation, cell cycle, DNA replication in vitro and tumor growth in vivo. HCG11 can raise p27 Kip1 expression via binding to miR-942-5p and IGF2BP2, and p27 Kip1 acts as a key effector for HCG11 exerting biological functions. In conclusion, HCG11 is downregulated in OS, and restrains OS growth both in vitro and in vivo by raising p27 Kip1 expression via binding to miR-942-5p and IGF2BP2.

Clinical short-term outcomes of articular-sided and bursal-sided partial-thickness rotator cuff tears of less than 50% in a single surgeon series: A protocol of randomized controlled trial.

BACKGROUND: There have been no published randomized clinical trial to assess the clinical outcomes between the articular-sided and bursal-sided tears. Therefore, a comparative analysis of evaluating and comparing the functional outcomes following arthroscopic repair of bursal-sided versus articular-sided partial-thickness rotator cuff tearsis essential. METHODS: This study is a present randomized controlled trial which is conducted in our hospital. Consecutive patients with symptomatic articular-sided or bursal-sided partial-thickness rotator cuff tears underwent arthroscopic repair between June 2020 and January 2022. The institutional review board approved the study proposal (with number 10012030), and informed consent was obtained from all patients. Inclusion criteria were existence of an articular- or bursal-sided tear involving <50% of the tendon thickness-confirmed intraoperatively and treated with arthroscopic debridement with or without other decompression surgery (acromioplasty/distal clavicle resection)-and a minimum follow-up of 2 years. All patients followed the same postoperative rehabilitation program. The patients were assessed at baseline preoperatively, and at 1 year and 2 years postoperatively. Outcome parameters were measured at each respective follow-up, which included active range of motion in forward flexion and abduction of the affected shoulder, pain score as measured on the Numeric Pain Rating Scale, as well as outcome scores in terms of the Constant-Murley Score, and Oxford Shoulder Score. RESULTS: Table 1 and Table 2 describe the data indicators that this article wants to evaluate and collect. CONCLUSIONS: We hypothesize that both groups of patients will show improvement in range of motion, functional outcome scores, and pain at 2 years, and that results would be similar between the two groups. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6496).

Association of the presence and its types of lamina fractures with posterior dural tear and neurological deficits in traumatic thoracic and lumbar burst fractures.

INTRODUCTION: The appropriate and optimal treatment for thoracic and lumbar (TL) burst fractures remains a topic of debate. Characterization of vertical laminar fractures (coronal cross-sectional imaging) is presented in this study to determine the severity and treatment options in TL burst fractures. METHODS: A retrospective evaluation of 341 consecutive patients with TL burst fractures was divided into Group I (whole), Group II (partial), and Group III (intact) based on the vertical laminar fracture morphology from coronal images on computed tomography (CT) scans. The presence of preoperative neurological status was reviewed, and several radiological parameters were measured. In addition, the incidence of dural tears was calculated in patients that underwent a decompression with posterior approach. RESULTS: In total, 270 lumbar and 71 thoracic burst fractures were analyzed. Compared with the intact group, the two other groups had significantly shorter central canal distance, wider interpedicular distance, and smaller spinal canal area, in particular, Group III. The incidences of preoperative neurological deficits in Groups I to III were 63.0, 22.2, and 6.3%, respectively. The incidences of dural tears in Groups I to III were 25.6, 6.3, and 0%, respectively. CONCLUSION: The morphology of vertical laminar fractures observed across the coronal plane was important. Patients with "whole", "partial" and "intact" laminar fractures indicated different severity of TL burst fractures. Due to the high probability of dural tears, decompression is recommended as a primary intervention for patients with "whole" laminar fractures. However, for patients without vertical laminar fractures, minimally invasive technique might be a better choice to avoid approach-related complications.

Less mechanical loading attenuates osteoarthritis by reducing cartilage degeneration, subchondral bone remodelling, secondary inflammation, and activation of NLRP3 inflammasome.

AIMS: Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. METHODS: A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our radiographs showed that joint space was significantly enlarged in rats with less mechanical loading. Moreover, cartilage destruction was attenuated in the less mechanical loading group with lower histological damage scores, and lower expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13. In addition, subchondral bone abnormal changes were ameliorated in OA rats with less mechanical loading, as reduced bone mineral density (BMD), bone volume/tissue volume (BV/TV), and number of osteophytes and osteoclasts in the subchondral bone were observed. Finally, the level of serum inflammatory cytokines was significantly downregulated in the less mechanical loading group compared with the normal mechanical loading group, as well as the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), caspase-1, and interleukin 1ß (IL-1ß) in the cartilage. CONCLUSION: Less mechanical loading alleviates cartilage destruction, subchondral bone changes, and secondary inflammation in OA joints. This study provides fundamental insights into the benefit of non-weight loading rest for patients with OA. Cite this article: Bone Joint Res 2020;9(10):731-741.

Effect of different geometrical structure of scapula on functional recovery after shoulder arthroscopy operation.

BACKGROUND: There are no published studies of the influence of geometry of the scapula on the postoperative recovery of rotator cuff injuries. Our aim was to explore the relationship between the critical shoulder angle (CSA), acromion index (AI), glenoid inclination (GI), and postoperative repair outcomes in shoulder joints after arthroscopic supraspinatus tendon repair. METHODS: Sixty two patients suffering a supraspinatus tear were analyzed retrospectively following failure of conservative treatment and subsequent shoulder arthroscopy in our hospital. Standard anterior and posterior X-rays of the injured shoulder had been performed prior to surgery, with follow ups for at least 2 years (24-43 months). Magnetic resonance imaging (MRI) was performed 2 years after surgery to assess repair of the supraspinatus tendon. Patients were divided into either the intact or re-tear group, according to the MRI results. In addition, assessments using the Constant Shoulder Score (CSS), the American Shoulder and Elbow Surgeon (ASES) Shoulder Assessment Form, the University of California at Los Angeles (UCLA) score and visual analog scale (VAS) score were performed to establish shoulder function at the 2-year evaluation for each patient. RESULTS: The mean CSA of all patients was 35.79° ± 3.59°, mean AI was 0.72 ± 0.05, and mean GI was 15.87° ± 3.62°. The CSA, AI, and GI in the intact group were statistically significantly different than the re-tear group (p < 0.05). There was no correlation between the magnitude of the CSA, AI, or GI and any shoulder function score (p > 0.05). CONCLUSIONS: The geometry of the scapula had no significant effect on the recovery of postoperative function of patients with rotator cuff injury, but the value of the CSA, AI, and GI affected the risk of rotator cuff re-tear.

Parosteal ossifying lipoma of the clavicle: A case report.

Lipomas are very common benign adipose tissue tumors that most often develop in subcutaneous tissue. A limited number of studies have described the characteristics of parosteal ossifying lipomas located in the fibula, cervical vertebrae and mandible. However, to the best of our knowledge, parosteal ossifying lipoma of the clavicle has not yet been reported. We herein describe the clinical symptoms, radiological and histological findings in a rare case of parosteal ossifying lipoma of the clavicle in a 40-year-old male patient. The characteristic histological appearance, together with computed tomography and/or magnetic resonance imaging characteristics, should aid in the accurate diagnosis of such cases.

[Early total care pattern for intertrochanteric fracture of femur in the elderly].

OBJECTIVE: To evaluate clinical results of early total care (ETC) treatment for elderly patients with intertrochanteric femur fractures. METHODS: Clinical data of 106 elderly patients with intertrochanteric fracture treated from January 2012 and February 2015 were retrospectively studied. According to whether receiving the early total care mode, the patients were divided into 2 groups, 34 cases were diagnosed and treated with early total care pattern (ETC group), including 14 males and 20 females with an average age of (74.88 ± 4.38) years old ranging from 70 to 86. According to Evans types, 4 cases were type I, 5 cases were type II, 13 cases were type III, 11 cases were type IV, 1 case was type V. Seventy-two patients were treated with conventional trauma method (conventional group), including 35 males and 37 females with an average age of (74.46 ± 3.63) years old ranging from 70 to 85. According to Evans type, 8 cases were type I ,13 cases were type II, 25 cases were type III, 25 cases were type IV, and 1 case was type V. All fractures were treated with proximal femoral nails anti-rotation (PFNA). Operative time, hospital stays, leaving bed time, complications, cases of death at 1 year after operation, postoperative Harris score at 12 months were observed and compared. RESULTS: All patients were followed up, the time of ETC group ranged from 9 to 18 months with an average of 13.29 ± 1.51, and the time in conventional group ranged from 12 to 16 months with an average 12.93 ± 1.15, while there was no significant difference between two groups in time of following-up (t = 1.368, P = 0.174). There was no significant meaning in cases of death between ETC group (2 cases) and conventional group (8 cases). Three cases occurred complications in ETC group, and 20 cases in conventional group,there was obvious meaning between two groups (χ² = 0.739, P = 0.318). Operative time,hospital stays,leaving bed time in ETC group respectively was (2.03 ± 0.67) d, (15.41 ± 2.87) d and (3.62 ± 0.74) d; while in conventional group respectively was (4.17 ± 1.59) d, (20.11 ± 4.24) d and (5.35 ± 1.22) d; there were significant differences between two groups in operative time, hospital stays, leaving bed time. Postoperative Harris scores at 12 months in ETC group was (82.32 ± 4.56), and (79.24 ± 5.52) in conventional group, there was obvious meaning between two groups (t = 2.833, P = 0.006). CONCLUSION: ETC pattern is a novel method for diagnosis and treatment of intertrochanteric femur fractures in elderly, it could shorten operative time, hospital stays, leaving bed time, decrease complications and promote recovery of function.

Adenovirus-mediated osteoprotegerin ameliorates cartilage destruction by inhibiting proteoglycan loss and chondrocyte apoptosis in rats with collagen-induced arthritis.

Our aim is to elucidate the effects of osteoproteogerin (OPG) on cartilage destruction in rats as a model of collagen-induced arthritis (CIA). To establish the CIA model, Sprague Dawley rats were injected with bovine type II collagen solution subcutaneously via the tails. Adenovirus-mediated OPG (Ad-OPG) was then injected intra-articularly either at the beginning of CIA (early OPG treatment) or one week after CIA establishment (late OPG treatment); vehicle or Ad-green fluorescent protein were injected as controls. The rats were killed 4 weeks after treatment. Ankle-joint sections were obtained for histology. Serum samples were collected for enzyme-linked immunosorbent assay. Safranin O staining showed that proteoglycan loss was inhibited in the early and late Ad-OPG groups. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining revealed that both early and late Ad-OPG treatments significantly prevented chondrocyte apoptosis in CIA rats. Furthermore, disintegrin and metalloproteinase with thrombospondin motif-5 expression decreased remarkably in the early and late OPG treatment groups. However, the cartilage destruction score, cartilage oligomeric matrix protein level and caspase-3 expression were only decreased in the early Ad-OPG treatment group. Additionally, ankle-joint swelling and the interleukin-1ß expression level in CIA rats were not notably altered by Ad-OPG treatment. Taken together, our results suggest that early Ad-OPG treatment has potent protective effects against cartilage destruction during rheumatoid arthritis progression, mainly by reducing proteoglycan loss and chondrocyte apoptosis.

N-acetylcysteine treatment following spinal cord trauma reduces neural tissue damage and improves locomotor function in mice.

Following spinal cord trauma, mitochondrial dysfunction associated with increased oxidative stress is a critical event leading to leukocyte inflammatory responses, neuronal cell death and demyelination, contributing to permanent locomotor and neurological disability. The present study demonstrated that the mitochondrial enhancer N-acetylcysteine (NAC) may restore redox balance via enhancement of mitochondrial respiratory activity following traumatic spinal cord injury (SCI). In addition, NAC ameliorates oxidative stress-induced neuronal loss, demyelination, leukocyte infiltration and inflammatory mediator expression and improves long-term locomotor function. Furthermore, neuronal survival and neurological recovery are significantly correlated with increased mitochondrial bioenergetics in SCI following treatment with NAC. Therefore, NAC may represent a potential therapeutic agent for preserving mitochondrial dynamics and integrity following traumatic SCI.

Targeting endothelin receptors A and B attenuates the inflammatory response and improves locomotor function following spinal cord injury in mice.

After spinal cord injury (SCI), the disruption of blood-spinal cord barrier by activation of the endothelin (ET) system is a critical event leading to leukocyte infiltration, inflammatory response and oxidative stress, contributing to neurological disability. In the present study, we showed that blockade of ET receptor A (ETAR) and/or ET receptor B (ETBR) prevented early inflammatory responses directly via the inhibition of neutrophil and monocyte diapedesis and inflammatory mediator production following traumatic SCI in mice. Long-term neurological improvement, based on a series of tests of locomotor performance, occurred only in the spinal cord­injured mice following blockade of ETAR and ETBR. We also examined the post­traumatic changes of the micro-environment within the injured spinal cord of mice following blockade of ET receptors. Oxidative stress reflects an imbalance between malondialdehyde and superoxide dismutase in spinal cord­injured mice treated with vehicle, whereas blockade of ETAR and ETBR reversed the oxidation state imbalance. In addition, hemeoxygenase-1, a protective protease involved in early SCI, was increased in spinal cord­injured mice following the blockade of ETAR and ETBR, or only ETBR. Matrix metalloproteinase-9, a tissue-destructive protease involved in early damage, was decreased in the injured spinal cord of mice following blockade of ETAR, ETBR or a combination thereof. The findings of the present study therefore suggested an association between ETAR and ETBR in regulating early pathogenesis of SCI and determining the outcomes of long­term neurological recovery.

Osteoprotegerin promotes the proliferation of chondrocytes and affects the expression of ADAMTS-5 and TIMP-4 through MEK/ERK signaling.

The involvement of osteoprotegerin (OPG) in bone metabolism has previously been established; however, whether OPG regulates chondrocytes directly and exerts precise cellular and molecular effects on chondrocytes remains to be determined. Thus, the present study aimed to investigate the direct effect of OPG on the viability, proliferation and functional consequences of chondrocytes. Primary chondrocytes were isolated from the knee of Sprague-Dawley rats. Passage 1 chondrocytes were identified by toluidine blue staining and used in the experiments. The cell proliferation induced by OPG at various concentrations was measured by a Cell Counting kit-8 (CCK-8) assay. Following pretreatment with mitogen-activated/extracellular signal-regulated kinase kinase (MEK) inhibitor U0126, extracellular signal-regulated kinase (ERK) inhibitor PD098059, and P38 mitogen-activated protein kinase (P38MAPK) inhibitor SB203580 for 30 min, chondrocytes were treated with OPG, and CCK-8 was performed. The cellular signals of MAPKs, including ERK, P38MAPK and c-Jun N-terminal protein kinase (JNK), were investigated by western blot analysis following treatment with OPG. The functional consequences following treatment with soluble OPG were analyzed by qPCR and western blot analysis. OPG increased chondrocyte proliferation with maximal effect at 10 ng/ml, and induced the phosphorylation of MEK and ERK but not P38MAPK or JNK. Suppression of ERK activity via PD098095 inhibited OPG-induced chondrocyte proliferation. Administration of OPG significantly downregulated ADAMTS­5 and upregulated tissue inhibitor of metalloproteinase (TIMP)-4 production, but had no effect on the expression of TIMP-1, -2 and -3, insulin-like growth factor I, transforming growth factor-ß, basic fibroblast growth factor, bone morphogenetic protein-2, collagen II, aggrecan and ADAMTS-4. Suppression of ERK activity via PD098095 inhibited the alteration of ADAMTS-5 and TIMP-4 expression induced by OPG. OPG therefore regulated the proliferation of chondrocytes via MEK/ERK signaling, and directly affected chondrocytes by influencing the expression profile of ADAMTS-5 and TIMP-4.