Recently, noncoding RNAs have been thought to play important roles in the sporadic occurrence of spinal deformity of adolescent idiopathic scoliosis (AIS). As a prognostic factor for curve progression, low bone mass has been hypothesized to crosstalk with AIS pathogenesis. Abnormal osteoblasts activities are reported in AIS without a clear mechanism. In this study, bone biopsies from patients with AIS and control subjects and the primary osteoblasts derived from those samples were used to identify the potential microRNA (miRNA) candidates that interfere with osteoblasts and osteocytes function. Microarray analysis identified miRNA-145-5p (miR-145) as a potential upstream regulator. miR-145 and β-catenin mRNA ( CTNNB1) were overexpressed in AIS bone tissues and primary osteoblasts, and their expression correlated positively in AIS. Knockdown of miR-145 restored impaired osteocyte activity through the down-regulation of active β-catenin expression and its transcriptional activity. Significant negative correlations between circulating miR-145 and serum sclerostin, osteopontin, and osteoprotegerin were noted in patients with AIS, which was in line with our cellular findings. This is the first study to demonstrate the effect of aberrant miRNA expression and its effect on osteocyte function in AIS, which may contribute to the low bone mass. Our findings also provide insight into the development of circulating microRNAs as a bone quality biomarker or even a prognostic biomarker for AIS.-Zhang, J., Chen, H., Leung, R. K. K., Choy, K. W., Lam, T. P., Ng, B. K. W., Qiu,Y., Feng, J. Q., Cheng, J. C. Y., Lee, W. Y. W. Aberrant miR-145-5p/β-catenin signal impairs osteocyte function in adolescent idiopathic scoliosis.

Congenital muscular torticollis (CMT) is a common musculoskeletal abnormality in children, which has been characterized by unclarified pathological changes in the sternocleidomastoid muscle (SCM) and various hypothetical etiologies. There are 2 main hypothetical etiologies for CMT in the literature: 1 infers that CMT may represent the sequela of an intrauterine or perinatal compartment syndrome, and the other regard CMT as a maldevelopment of the fetal SCM.To better understand the etiopathogenesis of CMT, we screened the necks of 1-day-old newborns that may potentially have CMT for evidence of SCM trauma or tumor.A convenience sample of 2564 full-term (>37 weeks) Chinese neonates were included in this study. All neonates were screened for CMT by physical examination at birth. If CMT was suspected, further ultrasonic and physical examinations were performed. When CMT was confirmed, we provided appropriate interventions and follow-up. The progress and changes in patients with CMT were recorded.Following physical examination, 44 of 2564 neonates were diagnosed with suspected CMT based on obvious facial asymmetry or palpable swelling or mass in the SCM. Among these, ultrasound examination showed 81.8% (36/44) had asymmetry in the thickness of the bilateral SCM. The 36 neonates were followed-up for 6 months; among them, 1 infant developed CMT and 35 showed normal development in bilateral SCM. The 1 patient with CMT underwent regular physiotherapy and recovered with no evidence of recurrence after the final 3 years of follow-up. No neonates suffered from signs of neck trauma, such as hematoma or subcutaneous ecchymosis.There was no evidence of neck trauma in this 1 day old newborn. The pseudotumor of SCM that developed after birth underwent differentiation, maturation, and disappeared as the baby grew. The SCM asymmetry did exist in some of the newborn babies, and became symmetric with the baby's growth. Data from this clinical study and our previous ultra-structural pathological studies suggested that both prenatal and postnatal factors play important roles in CMT. We hypothesized that CMT might be a developmental disease.

Adolescent idiopathic scoliosis is a complex disease with unclear etiopathogenesis. Systemic and persistent low bone mineral density is an independent prognostic factor for curve progression. The fundamental question of how bone quality is affected in AIS remains controversy because there is lack of site-matched control for detailed analysis on bone-related parameters. In this case-control study, trabecular bone biopsies from iliac crest were collected intra-operatively from 28 severe AIS patients and 10 matched controls with similar skeletal and sexual maturity, anthropometry and femoral neck BMD Z-score to control confounding effects. In addition to static histomorphometry, micro-computed tomography (μCT) and real time-PCR (qPCR) analyses, individual trabecula segmentation (ITS)-based analysis, finite element analysis (FEA), energy dispersive X-ray spectroscopy (EDX) were conducted to provide advanced analysis of structural, mechanical and mineralization features. μCT and histomorphometry showed consistently reduced trabecular number and connectivity. ITS revealed predominant change in trabecular rods, and EDX confirmed less mineralization. The structural and mineralization abnormality led to slight reduction in apparent modulus, which could be attributed to differential down-regulation of Runx2, and up-regulation of Spp1 and TRAP. In conclusion, this is the first comprehensive study providing direct evidence of undefined unique pathological changes at different bone hierarchical levels in AIS.