Tanshinone IIA promotes osteogenic differentiation potential and suppresses adipogenic differentiation potential of bone marrow mesenchymal stem cells.

Tanshinone IIA (Tan IIA) may have therapeutic effects on avascular necrosis of the femoral head (ANFH) by targeting bone marrow mesenchymal stem cells (BMSCs). The effect and underlying mechanism of Tan IIA on adipogenesis and osteogenesis ability of BMSCs remain to be elucidated. In the present study BMSCs were treated with osteogenic or adipogenic differentiation medium with or without Tan IIA under hypoxic environment. Osteogenic differentiation potential was evaluated by alkaline phosphatase (ALP) measurement, alizarin red staining and reverse transcription­quantitative (RT­q) PCR of osteogenic marker genes. Adipogenic differentiation potential was evaluated with oil red staining and RT­qPCR of adipogenic marker genes. Detailed mechanism was explored by RNA­seq and small molecular treatment during osteogenesis and adipogenesis of BMSCs. ALP level, mineralized nodules and expression level of osteogenic marker genes significantly increased following Tan IIA treatment during osteogenic differentiation of BMSCs. Lipid droplet and expression levels of adipogenic marker genes significantly decreased following Tan IIA treatment during adipogenic differentiation of BMSCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of RNA­seq data indicated increased Akt and TGFß signaling following Tan IIA treatment. Further western blot assay confirmed that Tan IIA significantly activated Akt/cAMP response element­binding protein signaling and TGFß/Smad3 signaling. Application of Akti1/2 (an Akt inhibitor) significantly decreased the promotion effect of osteogenesis induced by Tan IIA, while the addition of SB431542 significantly reduced inhibition effect of adipogenesis caused by Tan IIA. Tan IIA could promote osteogenic differentiation potential of BMSCs by activating AKT signaling and suppress adipogenic differentiation potential of BMSCs by activating TGFß signaling.

Postoperative dysesthesia after PVCR without anterior support applied in Yang's type A severe spinal kyphoscoliosis.

Backgrounds: The incidence and characteristics of postoperative dysesthesia (POD) have not been reported for posterior vertebral column resection (PVCR) in the treatment of severe spinal kyphoscoliosis. Objective: The objective of the study is to investigate the incidence and characteristics of POD in PVCR without anterior support applied in Yang's type A severe spinal kyphoscoliosis. Material and methods: From August 2010 to December 2019, 167 patients diagnosed with Yang's type A severe spinal kyphoscoliosis who underwent PVCR without anterior support applied were retrospectively reviewed. All the patients were monitored using five modes of intraoperative multimodal neurophysiological monitoring. Neuromonitoring data, radiographic parameters, and neurological complications were reviewed and analyzed. The incidence and characteristics of POD were further summarized. POD was defined as dysesthetic pain or burning dysesthesia which could be caused by spinal cord kinking or dorsal root ganglion (DRG) injury but with no motor deficits. Results: PVCR without anterior support was successfully conducted in all 167 patients. Intraoperative monitoring events occurred in five patients. One out of these five patients showed postoperative spinal cord injury (Frankel level C) but completely recovered within 9 months postoperation (Frankel level E). The number of levels and osteotomy space for vertebra resection were 1.28 and 3.6 cm, respectively. POD was confirmed in three patients (3/167, 1.8%), characterized as kyphosis with the apex vertebrae in T12 with the kyphotic Cobb angles of 100°, 115°, and 122°, respectively. The osteotomy space of vertebra resection in these three patients were 3.9, 3.8, and 4.2 cm, respectively. After the treatment by drug administration, they reported pain relief for 12-36 days. The pain gradually moved to the distal end of a proper DRG innervated region near the end. Conclusions: In this study, the incidence rate of POD in Yang's type A severe spinal kyphoscoliosis patients who underwent PVCR without anterior support applied was 1.8% (3/167). Evoked potential monitoring could not detect the occurrence of POD. POD in Yang's type A severe spinal kyphoscoliosis after PVCR could be ascribed to spinal cord kinking and DRG injury.