A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate.

Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification1. However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth1,2, but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.

Digitalization of the IOM: A comprehensive cadaveric study for obtaining three-dimensional models and morphological properties of the forearm's interosseous membrane.

State-of-the-art of preoperative planning for forearm orthopaedic surgeries is currently limited to simple bone procedures. The increasing interest of clinicians for more comprehensive analysis of complex pathologies often requires dynamic models, able to include the soft tissue influence into the preoperative process. Previous studies have shown that the interosseous membrane (IOM) influences forearm motion and stability, but due to the lack of morphological and biomechanical data, existing simulation models of the IOM are either too simple or clinically unreliable. This work aims to address this problematic by generating 3D morphological and tensile properties of the individual IOM structures. First, micro- and standard-CT acquisitions were performed on five fresh-frozen annotated cadaveric forearms for the generation of 3D models of the radius, ulna and each of the individual ligaments of the IOM. Afterwards, novel 3D methods were developed for the measurement of common morphological features, which were validated against established optical ex-vivo measurements. Finally, we investigated the individual tensile properties of each IOM ligament. The generated 3D morphological features can provide the basis for the future development of functional planning simulation of the forearm.