No abstract

Therapeutic study, Level V (expert opinion). See the Guidelines for Authors for a complete description of levels of evidence.

Aging or injury leads to degradation of the cartilage matrix and the development of osteoarthritis (OA). Because of a paucity of single-cell studies of OA cartilage, little is known about the interpatient variability in its cellular composition and, more importantly, about the cell subpopulations that drive the disease. Here, we profiled healthy and OA cartilage samples using mass cytometry to establish a single-cell atlas, revealing distinct chondrocyte progenitor and inflammation-modulating subpopulations. These rare populations include an inflammationamplifying (Inf-A) population, marked by interleukin-1 receptor 1 and tumor necrosis factor receptor II, whose inhibition decreased inflammation, and an inflammation-dampening (Inf-D) population, marked by CD24, which is resistant to inflammation. We devised a pharmacological strategy targeting Inf-A and Inf-D cells that significantly decreased inflammation in OA chondrocytes. Using our atlas, we stratified patients with OA in three groups that are distinguished by the relative proportions of inflammatory to regenerative cells, making it possible to devise precision therapeutic approaches. RESULTS High-dimensional mass cytometry-based profiling of normal and OA cartilageToward our goal of profiling rare stem/progenitor-like populations within normal and OA cartilage, we used cyTOF, a mass spectrometrybased high-dimensional method for single-cell detection of isotopelabeled antibodies (Fig. 1A) (8). While cyTOF panels have to be preselected for each experiment, this technique provides the advantage , Single-cell mass cytometry reveals cross-talk between inflammation-dampening and inflammation-amplifying cells in osteoarthritic cartilage.

Total knee arthroplasty is a traditional surgical procedure aimed to restore function and relief pain in patients with severe knee osteoarthritis. Recently, many medial pivot knee systems were deigned to replicate the normal knee kinematic: a highly congruent medial compartment and a less conforming lateral tibial plateau characterize these devices. A slightly asymmetric soft tissue balancing is mandatory using medial pivot designs to obtain a correct and physiological knee biomechanics leading good outcomes and long survival rates. This article describes a new surgical technique using a modern third generation TKA design combined with wireless load-sensor tibial trials to improve the correct knee load balancing with a minimal conformity of the polyethylene insert. The use of wireless load-sensing tibial trials has several benefits: it is an intraoperative, objective and dynamic tool allowing surgeons to optimize in real time soft tissue balancing. The meaning of a "truly balanced knee" is still a controversial issue in the current literature.