Cellular senescence is a phenotypic state that contributes to age‐related diseases through the secretion of matrix‐degrading and inflammatory molecules. An emerging therapeutic strategy for osteoarthritis (OA) is to selectively eliminate senescent cells by initiating apoptosis. This study establishes a cartilage explant model of senescence induction and senolytic clearance using p16Ink4a expression as a biomarker of senescence. Growth‐factor stimulation of explants increased the expression of p16Ink4a at both the mRNA and protein levels. Applying this culture system to cartilage from p16tdTom reporter mice (a knockin allele with tdTomato fluorescent protein regulated by the endogenous p16Ink4a promoter) demonstrated the emergence of a p16‐high population that was quantified using flow cytometry for tdTomato. Cell sorting was used to separate chondrocytes based on tdTomato fluorescence and p16‐high cells showed higher senescence‐associated β‐galactosidase activity and increased gene expression of the senescence‐associated secretory phenotype as compared with p16‐low cells. The potential for effective senolysis within the cartilage extracellular matrix was assessed using navitoclax (ABT‐263). Navitoclax treatment reduced the percentage of p16‐high cells from 17.9 to 6.1% (mean of 13 matched pairs; P < 0.001) and increased cleaved caspase‐3 confirmed apoptotic activity. Together, these findings establish a physiologically relevant cartilage explant model for testing the induction and elimination of senescent chondrocytes, which will support investigations of senolytic therapy for OA.—Sessions, G. A., Copp, M. E., Liu, J.‐Y., Sinkler, M. A., D'Costa, S., Diekman, B. O. Controlled induction and targeted elimination of p16INK4a‐expressing chondrocytes in cartilage explant culture. FASEB J. 33, 12364–12373 (2019). http://www.fasebj.org

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Background: Skeletal maturity estimation is central in the management of scoliosis and lower-limb deformity. Utilizing demographic characteristics and modern computing, we sought to create a reliable, rapid, and accurate method for measuring skeletal maturity on an elbow radiograph.Methods: Utilizing the Bolton-Brush Collection, 4 parameters from the modified Sauvegrain method and 7 novel parameters were screened. Ten parameters were evaluated on serial peripubertal elbow radiographs, using Greulich and Pyle (GP) skeletal age from corresponding hand radiographs as a comparison. Stepwise linear regression and generalized estimating equations were used to identify radiographic and demographic parameters for estimating skeletal maturity based on 90% of final height. The elbow system was compared with GP only; olecranon apophysis only; age, sex, and GP; age, sex, and olecranon apophysis; age, sex, and elbow system with anteroposterior and lateral parameters; age, sex, and elbow system with anteroposterior parameters; and age, sex, and elbow system with lateral parameters.Results: In this study, 367 radiographs from 77 patients (40 girls and 37 boys) were included. Following stepwise linear regression, 4 radiographic parameters were included in the anteroposterior and lateral elbow system; 3 were included in the anteroposterior elbow system; and 4 were included in the lateral elbow system. The lateral elbow system predicted skeletal maturity with a mean discrepancy of 0.41 year and produced similar mean discrepancies to GP with age and sex (0.42; p = 0.93), and it trended toward better performance than the olecranon apophysis system with age and sex (0.43; p = 0.06). The lateral elbow system had the lowest percent of outlier predictions >1 year discrepant from the skeletal maturity reference (4.6%), although it was only significantly better than the GP-only group (29.4%) and the olecranon apophysis-only group (21.0%) (p < 0.001 for both). Conclusions:We systematically developed a lateral elbow system that performed equivalently to GP using 4 simple parameters and trended toward outperforming the olecranon apophysis systems in skeletal maturity estimation. Future clinical validation will be necessary to understand the utility of this system.Clinical Relevance: The lateral elbow system may be a more accurate prediction of skeletal maturity compared with the previously described olecranon apophysis system and can be used to guide the management of many pediatric orthopaedic conditions.Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/H200).