Trim21 depletion alleviates bone loss in osteoporosis via activation of YAP1/β-catenin signaling

Despite the diverse roles of tripartite motif(Trim)-containing proteins in the regulation of autophagy,the innate immune response,and cell differentiation,their roles in skeletal diseases are largely unknown.We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast(OB)differentiation in osteosarcoma.However,how Trim21 contributes to skeletal degenerative disorders,including osteoporosis,remains unknown.First,human and mouse bone specimens were evaluated,and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients.Next,we found that global knockout of the Trim21 gene(KO,Trim2^(1-/-))resulted in higher bone mass compared to that of the control littermates.We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and elevating the activity of OBs;moreover,Trim21 depletion suppressed osteoclast(OC)formation of RAW264.7 cells.In addition,the differentiation of OCs from bone marrow-derived macrophages(BMMs)isolated from Trim21^(-/-)and Ctsk-cre;Trim21^(f/f)mice was largely compromised compared to that of the littermate control mice.Mechanistically,YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs.More importantly,the loss of Trim21 prevented ovariectomy(OVX)-and lipopolysaccharide(LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling.Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption,thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

The Clinical Outcomes of Transforaminal Percutaneous Endoscopic Discectomy in Treating Lumbar Disc Herniation: A Review

Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive technique started during the late 20th century. This process is done through microscopic view under local anesthesia. There is a growing but still insufficient evidence that lumbar EDS shows slightly better results in terms of minor tissue damage, shorter hospital stay, faster return to ordinary daily activities, and patient satisfaction. Recurrence rate still remains a matter of debate, and is related with the surgical skills of the surgeon. The complication rate seems to be similar in both of the techniques i.e., open and endoscopic. More randomized controlled trials, systematic reviews and meta-analysis are needed to clarify whether lumbar EDS can be considered comparable if not superior to standard open discectomy. In spite of lacking defined clinical evidence, lumbar EDS is without doubt a rapidly expanding PELD and its future developments are incredibly promising. Due to less complication rate this technique can be considered as a gold standard compared to the open discectomy. The surgeons still require more cadaveric practices for learning the curve and to approach the herniated disc area. The main objective of this review article is to show the clinical outcomes of the Transforaminal Percutaneous Endoscopic Discectomy in treating the lumbar disc herniation.

Protective effect of liposome-mediated glial cell line-derived neurotrophic factor gene transfer in vivo on motoneurons following spinal cord injury in rats

Objective: To investigate the effect of liposome-mediated glial cell line-derived neurotrophic factor (GDNF) gene transfer in vivo on spinal cord motoneurons after spinal cord injury (SCI) in adult rats. Methods: Sixty male Sprague-Dawley rats were divided equally into two groups: GDNF group and control group. The SCI model was established according to the method of Nystrom, and then the DC-Chol liposomes and recombinant plasmid pEGFP-GDNF cDNA complexes were injected into the injured spinal cord. The expression of GDNF cDNA 1 week after injection was detected by RT-PCR and fluorescence microscope. We observed the remaining motoneurons in the anterior horn and the changes of cholinesterase (CHE) and acid phosphatase (ACP) activity using Nissl and enzyme histochemistry staining. The locomotion function of hind limbs of rats was evaluated using inclined plane test and BBB locomotor scale. Results: RT-PCR and fluorescence observation confirmed the presence of expression of GDNF cDNA 1 week and 4 weeks after injection. At 1, 2, 4 weeks after SCI, the number of motoneurons in the anterior horn in GDNF group ((20.4)±(3.2), (21.7)±(3.6), (22.5)±(3.4)) was more than that in control group ((16.8)±(2.8), (17.3)±(2.7), (18.2)±(3.2), P<(0.05)). At 1, 2 weeks after SCI, the mean gray of the CHE-stained spinal motoneurons in GDNF group ((74.2)±(25.8), (98.7)±(31.6)) was less than that in control group ((98.5)±(32.2), (134.6)±(45.2), P<(0.01)), and the mean gray of ACP in GDNF group ((84.5)±(32.6), (79.5)±(28.4)) was more than that in control group ((61.2)±(24.9), (52.6)±(19.9), P<(0.01)). The locomotion functional scales in GDNF group were higher than that in control group within 1 to 4 weeks after SCI (P<(0.05)). Conclusions: GDNF gene transfer in vivo can protect motoneurons from death and degeneration induced by incompleted spinal cord injury as well as enhance locomotion functional restoration of hind limbs. These results suggest that liposome-mediated delivery of GDNF cDNA might be a practical method for treating traumatic spinal cord injury.