{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T22:37:48Z","timestamp":1762641468962},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,5,16]],"date-time":"2012-05-16T00:00:00Z","timestamp":1337126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heterotopic ossification or calcification follows any type of musculoskeletal trauma and is known to occur after arthroplasties of hip, knee, shoulder, or elbow; fractures; joint dislocations; or tendon ruptures. Histamine receptor H2 (Hrh2) has been shown to be effective for reducing pain and decreasing calcification in patients with calcifying tendinitis, which suggested that H2 blockers were effective for the treatment of tendon ossification or calcification. However, the detailed mechanisms of its action on tendon remain to be clarified. We investigated the mechanisms underlying H2 blocker\u2010mediated suppression of tendon calcification, with a focus on the direct action of the drug on tendon cells. Famotidine treatment suppressed the mRNA expressions of <jats:italic>Col10a1<\/jats:italic> and <jats:italic>osteocalcin<\/jats:italic>, ossification markers, in a tendon\u2010derived cell line TT\u2010D6, as well as a preosteoblastic one MC3T3\u2010E1. Both of the cell lines expressed Hrh2; histamine treatment induced <jats:italic>osteocalcin<\/jats:italic> expression in these cells. Famotidine administration suppressed calcification in the Achilles tendon of <jats:italic>ttw<\/jats:italic> mice, a mouse model of ectopic ossification. These data suggest that famotidine inhibits osteogenic differentiation of tendon cells in vitro, and this inhibition may underlie the anti\u2010calcification effects of the drug in vivo. This study points to the use of H2 blockers as a promising strategy for treating heterotopic ossification or calcification in tendon, and provides evidence in support of the clinical use of famotidine. \u00a9 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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