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Backgrounds: Abnormal vertebral growth and development have been found in adolescent idiopathic scoliosis (AIS) patients, and the proliferation and differentiation of bone development‐related cells play important roles in its pathogenesis. However, a comprehensive single‐cell‐level differentiation roadmap in AIS has not been achieved. Methods: The present study compared the single‐cell level cellular landscapes of spinal cancellous bone tissues between AIS patients and healthy subjects using high throughput single‐cell RNA sequencing (scRNA‐seq), which covers multiple cellular lineages including osteoblast, chondrocyte, osteoclast and related immunocytes. We constructed the differentiation trajectories of bone development‐related cell lineages through pseudotime analysis, and the intercellular‐communication networks between bone development‐related cells and immunocytes were further developed. Results: A total of 11 distinct cell clusters were identified according to the genome‐wide transcriptome profiles. t‐Distributed stochastic neighbor embedding (t‐SNE) analysis showed that mesenchymal stem cells (MSC) were classified into three subtypes: MSC‐LOXL2, MSC‐IGFBP5, and MSC‐GJA1. Gene ontology (GO) analysis showed that MSC‐GJA1 might possess greater osteoblast differentiation potential than the others. MSC‐IGFBP5 was the specific MSC subtype observed only in AIS. There were two distinct gene expression clusters: OB‐DPT and OB‐OLFML2B, and the counts of osteoblasts derived from AIS was significantly less than that of non‐AIS subjects. In AIS patients, MSC‐IGFBP5 failed to differentiate into osteoblasts and exhibited negative regulation of cell proliferation and enhanced cell death. CPC‐PCNA was found to be the specific chondrocyte progenitor cell (CPC) subtype observed only in AIS patients. The cell counts of OC‐BIRC3 in AIS were less than those in controls. Pseudotime analysis suggested two possible distinct osteoclast differentiation patterns in AIS and control subjects. Monocytes in AIS mainly differentiated into OC‐CRISP3. Conclusions: Our single‐cell analysis first revealed differences existed in the cellular states between AIS patients and healthy subjects and found the differentiation disruption of specific MSC and CPC clusters in AIS. Cell communication analysis provided the possible pathogenesis of osteoblast and chondrocyte differentiation dysfunction in AIS. [ABSTRACT FROM AUTHOR]

Abstract Background CALM1 gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the CALM1 core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population. Methods A case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects. Results No significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients. Conclusion The present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.

Background. Patients with spinal deformities and nerve compression due to spinal tuberculosis often require surgical intervention. The objective of this study was to assess the long-term therapeutic effectiveness of one-stage anterior debridement, bone grafting, and internal fixation for lower cervical tuberculosis with kyphosis. Methods. Twenty-one patients with lower cervical tuberculosis and cervical kyphosis received one-stage anterior debridement, autologous iliac bone grafting, and internal plate fixation. Patients were followed-up postoperatively for at least 5 years. Outcome measures included neck pain using Visual Analogue Scale (VAS) scores, Frankel classification of spinal cord injury, and Cobb angle of cervical kyphosis. Results. Eighteen patients had lesions in 2 vertebrae and 3 had lesions in 3 vertebrae. Cervical tuberculosis was cured in all patients. The mean preoperative VAS score for neck pain was 8 (range: 6-10), whereas the mean best postoperative VAS score was 0.6 (range: 0-3). Mean final VAS score was significantly higher than the best VAS score (2.14 vs. 0.62). Of the 13 patients with symptoms of spinal cord compression, 9 improved by 1 grade and 4 improved by 2 grades according to Frankel classification at final follow-up. The mean preoperative Cobb angle of cervical kyphosis was 29° (range: 15°-50°), whereas the mean postoperative Cobb angle at final follow-up was −1.8° (range: 2-7°). Conclusions. One-stage anterior debridement, bone grafting, and internal fixation can effectively remove lesions, decompress the nerve, reduce pain, and correct kyphosis in patients with cervical tuberculosis and associated kyphosis. Long-term postoperative outcomes were satisfactory. [ABSTRACT FROM AUTHOR]