Upregulated miR-125b mitigates inflammation, astrocyte activation, and dysfunction of spinal cord injury by inactivating the MAPK pathway.

BACKGROUND: Since the abnormal expression of miR-125b in spinal cord injury (SCI) and the regulatory effect of miR-125b on the MAPK pathway have been expounded, we attempt to investigate whether miR-125b exerts a regulatory effect on SCI by modulating the MAPK pathway. METHOD: A SCI rat model was established. The rats were treated with miR-125b antagomir or agomir, and their motor function affected by miR-125b was further detected by Basso-Beattie-Bresnahan (BBB) scoring. The histopathological changes and neuronal loss in the spinal cord were evaluated using hematoxylin-eosin and Nissl staining. Microglia-conditioned medium (MCM) was prepared and further used to treat the astrocytes, the activation of which was evaluated via immunofluorescence staining. The expressions of miR-125b, inflammation-related factors (IL-6, IL-1ß, TNF-α, and IL-10), and MAPK pathway-related proteins (p38, ERK1/2, and JNK1/2 as well as their phosphorylated (p) forms) in the spinal cord, serum, and MCM-treated astrocytes of rats were determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, and Western blot. RESULT: MiR-125b was lowly expressed in SCI-modeled rats. MiR-125b downregulation aggravated the impaired motor function, the disorder within the tissue, astrocyte activation, and neuron loss in the spinal cord tissues of SCI-modeled rats, while miR-125b upregulation did oppositely. MiR-125b downregulation enhanced the levels of IL-6, IL-1ß, TNF-α, p38, p-p38, p-ERK1/2, and p-JNK1/2, whilst reducing that of IL-10. Contrarily, miR-125b upregulation exerted the opposite effects in SCI-modeled rats and MCM-treated astrocytes. CONCLUSION: Up-regulation of miR-125b mitigates inflammation, astrocyte activation, and dysfunction in SCI by inactivating the MAPK pathway.

Downregulation of miR­146a inhibits osteoporosis in the jaws of ovariectomized rats by regulating the Wnt/ß­catenin signaling pathway.

MicroRNAs (miRNAs or miRs) play important roles in osteoporosis and exhibit high potential in the therapeutic treatment of this condition. The present study aimed to explore the effects of miR­146a on bone loss noted in the jawbones of ovariectomized (OVX) rats and the interaction of miR­146a with the Wnt/ß­catenin signaling pathway. OVX Sprague­Dawley female rats were used to establish the animal model of osteoporosis (OP). Bone mineral density (BMD) was measured via dual­energy X­ray and the miR­146a levels were detected by reverse transcription­quantitative PCR. miR­146a antagonist (miR­146a­A) and negative control (miR­146a­NC) were used to examine the effects of miR­146a on OVX rats. The contents of osteocalcin and tartrate resistant phosphatase (TRAP) were detected via ELISA. Hematoxylin and eosin, and TRAP staining were used to observe the pathological changes and the number of osteoclasts in the jawbone, respectively. In addition, the expression levels of the nuclear factor of activated T cells c1 (NFATc1), c­Fos and cathepsin K (CTK) in the jawbone were detected by immunohistochemistry, whereas the expression levels of osteoprotegerin, TRAP, dickkopf1, Wnt2 and ß­catenin in the same tissues were assessed by western blot analysis. The Wnt2 activator (DKK2­C2) and inhibitor (endostatin) were used to examine the effects of miR­146a on the Wnt/ß­catenin pathway. The results indicated that the BMD was increased, whereas the contents of osteocalcin and TRAP were decreased in the miR­146a­A group compared with those noted in the OP or negative control groups (P<0.05). Although the trabecular bone area of the OP group was decreased, the conditions were improved in the miR­146a­A group. The number of osteoclasts was decreased in the miR­146a­A group compared with that noted in the OP group (P<0.05). The expression levels of NFATc1, c­Fos and CTK in the miR­146a­A group were decreased compared with those noted in the OP or negative control groups (P<0.05). Similar results were found following the comparison of the miR­146a­A group with the DKK2­C2 group. Taken together, these data demonstrated that miR­146a downregulation inhibited OP of the jawbone in OVX rats by activating the Wnt/ß­catenin signaling pathway.

Concomitant ligamentous and meniscal injuries in floating knee.

BACKGROUND: To identify and characterize the concomitant ligamentous and meniscal injuries in floating knee. METHODS: A total of 37 cases of floating knee were enrolled. Arthroscopic or open surgical examination of the knee, Lachman test, posterior drawer's test, and varus and valgus stress tests under anesthesia were carried out to determine the incidence of knee injury. RESULTS: Through arthroscopic and open surgical examinations, a medial meniscal tear was detected in 14 (37.8%) cases and a lateral meniscal tear in 11 (29.7%). Twenty-one (56.8%) patients had anterior cruciate ligament (ACL) injury including complete injury in 6 and incomplete injury in 15 cases. Three (8.1%) patients had posterior cruciate ligament (PCL) tear, including complete injury in 1 and incomplete injury in 2. Varus and valgus stress tests revealed that 10 (27.0%) and 7 (18.9%) patients had medial and lateral collateral ligament (MCL and LCL) laxity, respectively. Lachman test showed positive in 8 (21.6%) cases. Posterior drawer test showed positive in 3 (8.1%) cases. Twenty-six (70.3%) patients had knee ligamentous injuries. ACL injury was the most common ligamentous injury. ACL injury in 15 (71.4%) cases was associated with meniscal injury, including medial meniscal injury in 9 (42.9%) and lateral meniscal injury in 6 (28.6%). CONCLUSION: Physicians should pay attention to the concomitant ligamentous and meniscal injuries in floating knee. Careful clinical examination with aid of arthroscopic examination is helpful for the early diagnosis and treatment of these injuries.