Hypoxia, a common environmental condition, influences cell signals and functions. Here, we compared the effects of hypoxia (1% oxygen) and normoxia (air) on chondrogenic differentiation of human mesenchymal stem cells (MSCs). For in vitro chondrogenic differentiation, MSCs were concentrated to form pellets and subjected to conditions appropriate for chondrogenic differentiation under normoxia and hypoxia, followed by the analysis for the expression of genes and proteins of chondrogenesis and endochondral ossification. MSCs induced for differentiation under hypoxia increased in chondrogenesis, but decreased in endochondral ossification compared to those under normoxia. MSCs induced for differentiation were more resistant to apoptosis under hypoxia compared to those under normoxia. The hypoxia-dependent protection of MSCs from chondrogenesis-induced apoptosis correlated with an increase in the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/FoxO pathway. These results suggest that the PI3K/Akt/FoxO survival pathway activated by hypoxia in MSCs enhances chondrogenesis and plays an important role in preventing endochondral ossification.
In Brief Study Design. To demonstrate the existence of mesenchymal stem cells (MSCs) in ligamentum flavum (LF) and their pathogenic role in LF hypertrophy. Objective. To isolate and characterize LF-derived MSCs and their response to transforming growth factor-beta 1 (TGF-β1) and trichostatin A (TSA), a histone deacetylase inhibitor (HDACi). Summary of Background Data. LF is a connective tissue, of which hypertrophic changes induce spinal stenosis. The pathogenic role of TGF-β1 in spinal stenosis has been implicated. TSA has been shown to suppress TGF-β1–induced alpha-smooth muscle actin (α-SMA), type I and III collagen synthesis in a variety of cells. MSCs have been isolated from a variety of adult tissues, except LF. Whether MSCs exist in LF and their response to TGF-β1 and TSA is not clear. Methods. The MSCs from LF were isolated and cultured. Their phenotypic character, linage differentiation potential, and response to TGF-β1 and TSA were analyzed. Results. LF-derived MSCs have the similar profile of surface markers as bone marrow MSCs. They were demonstrated to have the potential to be differentiated into osteoblasts, adipocytes, and chondrocytes. Administration of TGF-β1 stimulated cell proliferation, enhanced the gene expression of type I and III collagen, and increased the gene expression and protein level of α-SMA. TSA blocked the fibrogenic effects of TGF-β1. Conclusion. The current results demonstrated the isolation of MSCs from LF. The cellular response to TGF-β1 implied that these cells might play an important role in the pathogenesis of LF hypertrophy. TSA, which blocks the effects of TGF-β1, may be a potent therapeutic choice for inhibiting LF hypertrophy. Mesenchymal stem cells isolated from ligamentum flavum have self-renewal and multiple differentiation capacities. Their response to transforming growth factor-β1 (TGF-β1) implies that these cells play a pathogenic role in ligamentum flavum hypertrophy. Trichostatin-A, blocking the effects of TGF-β1, may be a potential therapeutic choice for ligamentum flavum hypertrophy.
This in vitro biomechanical study reports on a new implant, called an intravertebral expandable pillar (IVEP). The implant is aimed at restoring the height and strength of collapsed vertebra after fracture in an osteoporotic patient. The hypothesis is that the IVEP can effectively restore the body height of the compressed vertebra and provide proper stiffness for the collapsed vertebra. Although the reported complication rate of percutaneous vertebroplasty by injection of polymethylmethacrylate (PMMA) is low, the sequelae are severe; other potential adverse effects of PMMA injection into the vertebral body include thermal necrosis of the surrounding tissue caused by a high polymerization temperature, and lack of long-term biocompatibility. We test the mechanical properties before and after fracture of 14 human cadaver lumbar vertebrae by a material testing system. The fractured vertebra was implanted with the IVEP, and its mechanical properties tested. The vertebral body height at each stage was evaluated by a digital caliper and radiographic films. After IVEP implantation, the vertebral body height restoration rate was 97.8%. The vertebral body height lost 12.7% after the same loading to create fracture. The vertebra lost half of its strength after compressed fracture, while IVEP implantation restored 86.4% of intact vertebra strength. The stiffness of intact vertebrae was significantly greater than that of untreated vertebrae after fracture and fractured vertebrae with IVEP treatment, while the stiffness of fractured vertebrae after IVEP treatment was significantly greater than that of untreated vertebrae after fracture. The bipedicularly implanted IVEP restores the initial height and strength of the vertebral body following an induced compression fracture, and could be used by a minimally invasive procedure to treat lumbar vertebra compression factures and avoid the disadvantage of using bone cement in vertebroplasty or kyphoplasty.
Abstract Background Ankle syndesmosis injury is a common condition, and the injury mechanism can be sorted into pure syndesmosis injury, Weber-B, and Weber-C type fractures. This study aims to evaluate the treatment outcomes and stability of suture-button fixation for syndesmosis injury with different injury mechanisms. We hypothesized that injury mechanisms would alter the stability of suture-button fixation. Methods We retrospectively reviewed 63 patients with ankle syndesmosis injury who underwent surgery with TightRope (Arthrex, Naples, FL, USA) from April 2014 to February 2019. The stability of suture-button fixation with TightRope was evaluated by comparing the preoperative, postoperative, and final follow-up measurements of tibiofibular clear space (TFCS), tibiofibular overlap (TFO), and medial clear space (MCS). A subgroup analysis for each demographic group and injury type including pure syndesmosis injury, Weber-B, and Weber-C type fractures were performed. Results Syndesmosis was effectively reduced using TightRope. After the index surgery, the tibiofibular clear space was reduced from 7.73 to 4.04 mm, the tibiofibular overlap was increased from 3.05 to 6.44 mm, and the medial clear space was reduced from 8.12 to 3.54 mm. However, syndesmosis widening was noted at the final follow-up, especially in Weber-C type fractures (TFCS 3.82 to 4.45 mm, p < 0.01 and TFO 6.86 to 6.29 mm, p = 0.04). Though widened, the final follow-up values of tibiofibular clear space and tibiofibular overlap were in the acceptable range. Postoperatively and at the final follow-up, medial clear space was found to be significantly larger in the Weber-C group than in the pure syndesmosis and Weber-B groups ( p < 0.05). Conclusions Suture-button fixation can offer anatomic reduction and dynamic fixation in syndesmosis injuries. However, when using this modality for Weber-C type fractures, more attention should be focused on the accuracy of reduction, especially of medial clear space, and rediastasis should be carefully monitored. Trial registration This trial was retrospectively approved by TMU-JIRB. Registration number N202004122, and the date of approval was May 06, 2020. Level of evidence III
'/%3e%3cuse xlink:href='%23a' transform='rotate(60)'/%3e%3ccircle r='17' fill='%23000095'/%3e%3ccircle r='15' fill='%23fff'/%3e%3c/svg%3e)
