Temporal transcriptome features identify early skeletal commitment during human epiphysis development at single-cell resolution.

Human epiphyseal development has been mainly investigated through radiological and histological approaches, uncovering few details of cellular temporal genetic alternations. Using single-cell RNA sequencing, we investigated the dynamic transcriptome changes during post-conception weeks (PCWs) 15-25 of human distal femoral epiphysis cells. We find epiphyseal cells contain multiple subtypes distinguished by specific markers, gene signatures, Gene Ontology (GO) enrichment analysis, and gene set variation analysis (GSVA). We identify the populations committed to cartilage or ossification at this time, although the secondary ossification centers (SOCs) have not formed. We describe the temporal alternation in transcriptional expression utilizing trajectories, transcriptional regulatory networks, and intercellular communication analyses. Moreover, we find the emergence of the ossification-committed population is correlated with the COL2A1-(ITGA2/11+ITGB1) signaling. NOTCH signaling may contribute to the formation of cartilage canals and ossification via NOTCH signaling. Our findings will advance the understanding of single-cell genetic changes underlying fetal epiphysis development.

Measurement of femoral posterior condylar offset and posterior tibial slope in normal knees based on 3D reconstruction.

BACKGROUND: Femoral posterior condylar offset (PCO) and posterior tibial slope (PTS) are important for postoperative range of motion after total knee arthroplasty (TKA). However, normative data of PCO and PTS and the correlation between them among healthy populations remain to be elucidated. The purpose of this study was to determine PCO and PTS in normal knees, and to identify the correlation between them. METHODS: Eighty healthy volunteers were recruited. CT scans were performed followed by three-dimensional reconstruction. PCO and PTS were measured and analyzed, as well as the correlation between them. RESULTS: PTS averaged 6.78° and 6.11°, on the medial and lateral side respectively (P = 0.002). Medial PCO was greater than lateral (29.2 vs. 23.8 mm, P <  0.001). Both medial and lateral PCO of male were larger than female. On the contrary, male medial PTS was smaller than female, while there was no significant difference of lateral PTS between genders. There was an inverse correlation between medial PCO and PTS, but not lateral. CONCLUSIONS: Significant differences exhibited between medial and lateral compartments, genders, and among individuals. An inverse correlation exists between PCO and PTS in the medial compartment. These results improve our understanding of the morphology and biomechanics of normal knees, and subsequently for optimising prosthetic design and surgical techniques.