Apoptotic Body-Rich Media from Tenocytes Enhance Proliferation and Migration of Tenocytes and Bone Marrow Stromal Cells.

The intrinsic healing following tendon injury is ideal, in which tendon progenitor cells proliferate and migrate to the injury site to directly bridge or regenerate tendon tissue. However, the mechanism determining why and how those cells are attracted to the injury site for tendon healing is not understood. Since the tenocytes near the injury site go through apoptosis or necrosis following injury, we hypothesized that secretions from injured tenocytes might have biological effects on cell proliferation and migration to enhance tendon healing. Tenocyte apoptosis was induced by 24 h cell starvation. Apoptotic body-rich media (T-ABRM) and apoptotic body-depleted media (T-ABDM) were collected from culture media after centrifuging. Tenocytes and bone marrow-derived stem cells (BMDSCs) were isolated and cultured with the following four media: (1) T-ABRM, (2) T-ABDM, (3) GDF-5, or (4) basal medium with 2% fetal calf serum (FCS). The cell activities and functions were evaluated. Both T-ABRM and T-ABDM treatments significantly stimulated the cell proliferation, migration, and extracellular matrix synthesis for both tenocytes and BMDSCs compared to the control groups (GDF-5 and basal medium). However, cell proliferation, migration, and extracellular matrix production of T-ABRM-treated cells were significantly higher than the T-ABDM, which indicates the apoptotic bodies are critical for cell activities. Our study revealed the possible mechanism of the intrinsic healing of the tendon in which apoptotic bodies, in the process of apoptosis, following tendon injury promote tenocyte and stromal cell proliferation, migration, and production. Future studies should analyze the components of the apoptotic bodies that play this role, and, thus, the targeting of therapeutics can be developed.

Endoscopic Iliotibial Band Release During Hip Arthroscopy for Femoroacetabular Impingement Syndrome and External Snapping Hip Had Better Patient-Reported Outcomes: A Retrospective Comparative Study.

PURPOSE: To compare patient-reported outcomes (PROs) in patients with femoroacetabular impingement (FAI) syndrome and external snapping hip (ESH) treated with hip arthroscopy with or without endoscopic iliotibial band (ITB) release. METHODS: Retrospective review case series with both FAI syndrome and ESH who underwent surgical treatment under same indications. According to the primary operation that was determined by patients themselves, the patients undergoing ITB release during hip arthroscopy for FAI syndrome were enrolled in the ITB-R group, and patients undergoing hip arthroscopy without ITB release were enrolled in non-ITB-R group. Patients with dysplasia, severe osteoarthritis, revision, and bilateral surgery were excluded. PROs including international Hip Outcome Tool (iHOT-33), modified Harris Hip Score (mHHS), visual analog scale for pain (VAS-pain) and VAS-satisfaction, and the rates of achieving minimal clinically important difference, patient acceptable symptomatic state (PASS), and substantial clinical benefit for the PROs at 2 years operatively were comparative analyzed. RESULTS: The prevalence of ESH in patients with FAI syndrome who underwent hip arthroscopy in our institution was 4.9% (30 of 612 hips). The mean age at the time of surgery was 33.1 ± 6.9 years (range 22-48 years). After exclusion, 16 patients (16 hips) were enrolled into ITB-R group and 11 patients (11 hips) enrolled into non-ITB-R group. PROs including iHOT-33, mHHS, VAS-pain, and VAS-satisfaction in patients in ITB-R group were better than that in non-ITB-R group at 2 years postoperatively (P = .013, .016, .002, and .005, respectively). The rates of achieving PASS for mHHS, PASS for VAS-pain, and substantial clinical benefit for iHOT-33 of patients in ITB-R group were significantly better than that in non-ITB-R group (P = .009, .006, and .027, respectively). CONCLUSIONS: Patients with both FAI syndrome and ESH undergoing ITB release during hip arthroscopy had better PROs than those undergoing hip arthroscopy without ITB release. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Local anesthesia combined with intra-articular ropivacaine can provide satisfactory pain control in ankle arthroscopic surgery: A retrospective cohort study.

BACKGROUND: Local anesthesia (LA) is widely used in knee arthroscopic surgery but not in ankle arthroscopy. OBJECTIVE: To understand the effectiveness and safety of LA combined with ropivacaine in pain control for ankle arthroscopy. STUDY DESIGN: Retrospective cohort. METHODS: We retrospectively collected data for patients who underwent ankle arthroscopy from April 2012 to April 2017. Patients were grouped by anesthesia method: LA, LA with ropivacaine (LA+R), spinal anesthesia (SA), and SA with ropivacaine (SA+R). Intra- and postoperative visual analog scale (VAS) scores, complications, doses of supplemental pain medication, hospitalization cost and duration, and satisfaction with pain control during hospitalization were analyzed. RESULTS: The study included 276 patients (LA: 93; LA+R: 124; SA: 31; SA+R: 28). The LA and LA+R groups had significantly higher intraoperative VAS scores (LA vs. SA, p = 0.001; LA vs. SA+R, p = 0.002; LA+R vs. SA, p = 0.00; LA+R vs. SA+R, p = 0.00), but fewer complications, than the SA and SA+R groups. The LA+R and SA+R groups had significantly better outcomes for postoperative pain control (LA vs. LA+R, p = 0.01; LA vs. SA+R, p = 0.01; SA vs. SA+R, p = 0.01; SA vs. LA+R, p = 0.03) and required less supplemental pain medication. Hospitalization cost was lower and duration shorter in the LA and LA+R groups than in the SA and SA+R groups. There was no significant difference in satisfaction among the four groups. LIMITATIONS: This was a single-center retrospective and relatively short-term study. CONCLUSIONS: LA+R which could be safely applied in ankle arthroscopy provided satisfactory pain control, reduced postoperative pain intensity, fewer complications, shorter hospital stay, and good cost-effectiveness. It can be safely applied in ankle arthroscopy for the specific patients with ankle osteoarthritis.

[Experimental study of platelet-rich plasma in treatment of Achilles tendinopathy in rabbits].

OBJECTIVE: To explore the effect of platelet-rich plasma (PRP) in treatment of Achilles tendinopathy in rabbits, and provide experimental evidence for the clinical application of PRP in treatment of Achilles tendinopathy. METHODS: Forty-eight adult New Zealand white rabbits, weighing 2.5-3.0 kg, male or female, were randomly divided into model group (group A), model control group (group B), model+treatment control group (group C), model+treatment group (group D), with 12 in each group. The rabbits were injected with type Ⅰ collagenase to prepare Achilles tendinopathy models in groups A, C, and D, and with an equal dose of normal saline in group B. The blood from the central artery of rabbit ear was taken to preprare PRP by secondary centrifugation in group D. The results of platelet counts showed that PRP platelets reached 3 to 5 times the whole blood. After the model was prepared, the rabbits in groups C and D were injected with physiological saline and autologous PRP at the molding site respectively, once a week, 0.8 mL each time for 4 weeks. At 1 week after PRP injection, the relative hardness (expressed as HRD%) of Achilles tendon was evaluated by ultrasound elastic quantitative imaging detection technique; the maximum breaking load of Achilles tendon was measured by universal electronic tensile testing machine; the contents of collagen type Ⅰ and Ⅲ were determined by ELISA; and the morphology of Achilles tendon collagen fibers was observed by HE and Masson stainings. RESULTS: All animals survived during the experiment. The results of ultrasound elastic quantitative imaging and mechanical tests showed that the HRD% and the maximum breaking load were significantly lower in group A than in group B ( P<0.05) and in group C than in group D ( P<0.05). The results of ELISA showed that the content of collagen type Ⅰ was significantly lower in group A than in group B ( P<0.05) and in group C than in group D ( P<0.05); the content of collagen type Ⅲ was significantly higher in group A than in group B ( P<0.05) and in group D than in group C ( P<0.05). HE and Masson stainings showed that the Achilles tendon collagen fibers were irregularly curled and the structure was severely damaged in group A; the fibers were parallel and ordered, and the structure was complete in group B; the fibers were irregularly curled and structurally disordered in group C; the fibers were slightly curled and the structure was relatively complete in group D. CONCLUSION: A rabbit model of Achilles tendinopathy can be reconstructed by type Ⅰ collagenase injection. PRP treatment can increase the Achilles tendon hardness and maximum breaking load, up-regulate the expression level of collagen type Ⅰ and Ⅲ, improve the structure of Achilles tendon collagen fiber, and promote the repair in rabbit Achilles tendinopathy model.

MicroRNA-665 suppressed the invasion and metastasis of osteosarcoma by directly inhibiting RAB23.

MicroRNAs (miRNAs) are small, short and noncoding RNAs that regulate gene expression posttranscriptionally. Increasing evidences have demonstrated that deregulated expression of miRNAs is found in osteosarcoma. In this study, we demonstrated that miR-665 was downregulated in osteosarcoma tissues compared to non-tumorous tissues. The overall survival (OS) of osteosarcoma patients with low miR-665 expression was lower than that of these patients with high miR-665 expression. Ectopic expression of miR-665 suppressed the osteosarcoma cell proliferation, EMT and invasion. We identified Rab23 as a direct target gene of miR-665. Rab23 was downregulated in osteosarcoma tissues and cell lines. The expression of miR-665 was inversely associated with the expression of Rab23 in the osteosarcoma tissues. These results suggested that miR-665 acted as a tumor suppressor gene in the development of osteosarcoma.

Damage Control Orthopedics Management as Vital Procedure in Elderly Patients with Femoral Neck Fractures Complicated with Chronic Renal Failure: A Retrospective Cohort Study.

BACKGROUND: Chronic renal failure (CRF) predisposes to hip fractures in elderly patients, with high subsequent mortality. Selection and timing of the surgical procedure of such patients is a serious challenge. Many clinicians believe in earlier surgery as preferable and providing better outcomes. Damage control orthopedics (DCO) aids to adjust and optimize the overall condition of patients. METHODS: In 32 patients with femoral neck fractures complicated with CRF, we evaluated how the timing of the surgery determines the mortality rates if the DCO approach is applied. Preoperative ASA grading, POSSUM score, P-POSSUM score and DCO were carried out. Based on the assessment, timing of the surgery was ascertained. RESULTS: Of a total of 32 patients, twenty-nine patients were accepted for either early (< 48 hours; n = 18) or delayed (3-10 days; n = 10) surgery. Hip arthroplasty (total hip arthroplasty and hemiarthroplasty) was the principal surgery option. All patients survived operation and were followed up postoperatively with the average time of 30 days. Postoperative complications tended to occur at higher rates in the early vs. delayed surgery group (7/18 vs. 5/10). During follow up, a total of 3 patients died in both groups (2/18 in the early surgery and 1/10 in the delayed surgery group), mostly from multi-organ failures and acute respiratory distress syndrome. There was no significant difference in complication rates and Harris hip score between both groups. CONCLUSION: In patients with femoral neck fracture complicated with CRF, delaying the surgery for several days does not increase the incidence of postoperative adverse events.

Acemannan accelerates cell proliferation and skin wound healing through AKT/mTOR signaling pathway.

BACKGROUND: Acemannan is a bioactive polysaccharides promoting tissue repair. However, the roles of acemannan in skin wound healing and the underlying molecular mechanisms are largely unclear. OBJECTIVE: The goal of this study is to investigate the positive role of acemannan in cutaneous wound healing and its mechanism. METHODS: Mouse skin wound model and skin primary fibroblasts were used to demonstrate the positive effect of acemannan on cutaneous wound healing. The expressions of cell proliferation nuclear antigen ki-67, cyclin D1 and activity of AKT/mTOR signaling were analyzed in acemannan-treated fibroblasts and mice. Rapamycin and AKT inhibitor VIII were used to determine the key role of AKT/mTOR signaling in acemannan-promoting cutaneous wound healing. RESULTS: We found that acemannan significantly accelerated skin wound closure and cell proliferation. Acemannan promoted the expression of cyclin D1 in cultured fibroblasts, which was mediated by AKT/mTOR signal pathway leading to enhanced activity of the eukaryotic translation initiation factor-4F (eIF4F) and increased translation of cyclin D1. In contrast, pharmaceutical blockade of AKT/mTOR signaling by mTOR inhibitor rapamycin or AKT inhibitor VIII abolished acemannan-induced cyclin D1 translation and cell proliferation. In vivo studies confirmed that the activation of AKT/mTOR by acemannan played a key role in wound healing, which could be reversed by rapamycin. CONCLUSION: Acemannan promoted skin wound healing partly through activating AKT/mTOR-mediated protein translation mechanism, which may represent an alternative therapy approach for cutaneous wound.

Impaired wound healing results from the dysfunction of the Akt/mTOR pathway in diabetic rats.

BACKGROUND: Wound healing is impaired in diabetes mellitus. The underlying mechanism involved in this process is still unknown. The Akt/mTOR signaling pathway plays a crucial role in the pathogenesis of diabetes. OBJECTIVE: we investigated the role of the Akt/mTOR pathway in diabetic wounds and the mechanisms that growth factors activate this pathway to promote diabetic wound healing. METHODS: Full-thickness skin excisional wounds were created on the backs of normal and streptozotocin-induced diabetic rats. The expression of key proteins in the Akt/mTOR pathway was assayed using western blotting; topical effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on diabetic wounds and activation of the Akt/mTOR pathway were subsequently investigated. Activation of the Akt/mTOR pathway by GM-SCF in vitro was examined in rat primary fibroblasts. RESULTS: The results indicate that the Akt/mTOR pathway was activated in the wound tissue of both non-diabetic and diabetic rats, as indicated by a remarkable increase in expression of total and phosphorylated key proteins in this pathway. However, the expression level of these proteins was dramatically attenuated in diabetic wounds compared with non-diabetic wounds. Upon topical application of GM-CSF, the diabetic wound healing was remarkably improved concomitantly with increased expression and phosphorylation of key proteins in the Akt/mTOR pathway. In addition, rat fibroblast proliferation induced by GM-CSF depended on the Akt/mTOR pathway activation. CONCLUSION: Impaired wound healing results from the dysfunction of the Akt/mTOR pathway in diabetic rats. The pharmacologic elevation of this pathway may represent an attractive intervention strategy to improve prognosis of diabetic wounds.