Osteoarthritis is characterized by articular cartilage breakdown, and emerging evidence suggests that dysregulated innate immunity is likely involved. Here, we performed proteomic, transcriptomic, and electron microscopic analyses to demonstrate that mast cells are aberrantly activated in human and murine osteoarthritic joint tissues. Using genetic models of mast cell deficiency, we demonstrate that lack of mast cells attenuates osteoarthritis in mice. Using genetic and pharmacologic approaches, we show that the IgE/FcεRI/Syk signaling axis is critical for the development of osteoarthritis. We find that mast cell-derived tryptase induces inflammation, chondrocyte apoptosis, and cartilage breakdown. Our findings demonstrate a central role for IgE-dependent mast cell activation in the pathogenesis of osteoarthritis, suggesting that targeting mast cells could provide therapeutic benefit in human osteoarthritis.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

Restoration of the joint line of the knee during primary and revision total knee arthroplasty is a step that directly influences patient outcomes. In revision total knee arthroplasty, necessary bony landmarks may be missing or obscured, so there remains a lack of consensus on how to accurately identify and restore the joint line of the knee. In this study, 50 magnetic resonance images of normal knees were analyzed to determine a quantitative relationship between the joint line of the knee and 6 bony landmarks: medial and lateral femoral epicondyles, medial and lateral femoral metaphyseal flares, tibial tubercle, and proximal tibio-fibular joint. Wide variability was found in the absolute distance from each landmark to the joint line of the knee, including significant differences between the sexes. Normalization of the absolute distances to femoral or tibial diameters revealed reliable spatial relationships to the joint line of the knee. The joint line was found to be equidistant from the lateral femoral epicondyle and the proximal tibio-fibular joint, representing a reproducible point of reference for joint line restoration. The authors propose a simple 3-step algorithm that can be used with magnetic resonance imaging, computed tomography, or radiography to reliably determine the anatomical location of the joint line of the knee relative to the surrounding bony anatomy. [Orthopedics. 2016; 39(6):381-386.].

Periosteal response to injury varies with anatomical location, so conclusions from long bone studies should not be extrapolated for craniofacial applications. Murine maxillary periosteum has the osteogenic potential to induce vertical alveolar bone regeneration.