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• W3154336184 abstract "Purpose: Periostin (Postn) is a vitamin K-dependent and glutamate-containing matricellular protein in the fasciclin family. Postn was originally identified and characterized as osteoblast-specific factor 2 in murine osteoblasts. It is also found in the periosteum and collagen-dense fibrous connective tissues such as ligaments. Emerging evidence delineates that Postn is upregulated in patients with osteoarthritis (OA) and it has been identified as a gene of interest in articular cartilage. Expression of Postn is induced following joint trauma such as destabilization of the medial meniscus (DMM) and leads to OA. Recent data confirmed that the expression of Postn increases significantly in mouse and human OA cartilage and osteophytes. Immune-localization studies further revealed that Postn was present in the cartilage extracellular matrix. Mechanistically, addition of recombinant Postn protein to human or murine chondrocytes increases the expression of matrix metalloproteinase 13 (MMP-13). These findings clearly suggest a catabolic role of Postn in promoting cartilage degeneration in OA. Herein, we sought to better understand the role of Postn in OA development by assessing the functional impact of Postn deficiency in two murine models of experimental OA: DMM-induced post-traumatic OA model and aging-related spontaneous OA model. We hypothesize that genetic Postn loss-of-function in mice would protect against cartilage degeneration secondary to joint injury and aging. Methods: All procedures were approved by the Institutions’ Animal Care and Use Committee. Ten-week-old Postn-null (Postn−/−) mice on a B6-129S/J background and wild-type (B6-129S/J) male mice (n = 8-10 per genotype) were subjected to DMM surgery on the right hind limb under general anesthesia. Left hind limb served as a control. Mice were allowed to live for 8 weeks with unlimited food and water intake. Age-related spontaneous OA was analyzed in 24-month-old Postn−/− and wild-type mice (n = 6-7 per genotype). Knee joints were harvested and fixed in neutral buffered formalin. Prior to decalcification, knees were scanned using a micro-CT scanner to measure changes in various trabecular bone parameters. Knees were then decalcified and embedded in paraffin. Whole joint articular cartilage degeneration was assessed histologically using a well-established Osteoarthritis Research Society International (OARSI) scoring system on Safranin-O-stained sections. Serum levels of Postn were determined by solid-phase enzyme-linked immunosorbent assay. Expression of Postn and collagenase-3 (MMP-13) was measured by immunostaining. Non-parametric Mann-Whitney and Kruskal-Wallis tests were used to determine statistical differences with P < 0.05 considered statistically significant. Data are presented as mean value ± standard error of the mean. Results: Ten-week-old Postn−/− mice exhibited reduced cartilage degeneration relative to wild-type mice (Fig. 1A). Postn−/− mice had a significantly lower OARSI score compared with the wild-type mice (2.4 ± 0.7 vs. 4.0 ± 1.2; P = 0.011) as shown in Fig. 1B. Postn−/− mice displayed lower bone volume fraction (BV/TV), volumetric bone density, trabecular thickness and trabecular number, and higher trabecular spacing indicating protection from OA, compared to wild-type mice (Fig. 1C). Data from age-induced spontaneous OA revealed that 24-month-old Postn−/− mice had significantly less cartilage degeneration than wild-type mice (Fig. 2A). Postn−/− mice showed significantly lower OARSI score relative to wild-type mice (1.9±0.4 vs. 3.6±1.2; P = 0.014) indicating protection from cartilage degeneration and OA (Fig. 2B). Assessment of trabecular bone parameters in aged mice showed similar differences between the genotypes as noted above for the young DMM-operated mice (Fig. 2C). Postn−/−mice had negligible levels of serum Postn compared with wild-type (Fig. 3A). Immunofluorescent studies of cartilage indicated that Postn−/− mice expressed lower MMP-13 levels than wild-type mice (Fig. 3B). Conclusions: Taken together, findings from our study indicated that Postn deficiency protects against DMM-induced post-traumatic and age-related spontaneous OA. These findings demonstrate a common underlying mechanism of Postn deficiency in protecting against OA, independent of the cause. The inhibition/deletion of Postn represents a novel therapeutic target in the reduction of the severity of OA. Further studies are in progress to investigate the potential of Postn as a druggable target for the treatment of OA and its tissue-specific mechanistic role in OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)" @default.
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• W3154336184 date "2021-04-01" @default.
• W3154336184 modified "2023-09-27" @default.
• W3154336184 title "Periostin-null mice are protected from post-traumatic and age-related osteoarthrtis" @default.
• W3154336184 doi "https://doi.org/10.1016/j.joca.2021.02.136" @default.
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