Spondyloarthritis (SpA) is a chronic inflammatory disease that leads to ankylosis of the axial skeleton. Celecoxib (cyclooxygenase-2 inhibitor, COX-2i) inhibited radiographic progression in a clinical study of SpA, but in the following study, diclofenac (COX-2 non-selective) failed to show that inhibition. Our study aimed to investigate whether nonsteroidal anti-inflammatory drugs (NSAIDs) inhibited bone progression in SpA, and whether celecoxib had a unique function (independent of the COX-inhibitor), compared with the other NSAIDs. We investigated the efficacy of various NSAIDs in curdlan-injected SKG mice (SKGc), an animal model of SpA, analyzed by bone micro-CT and immunohistochemistry. We also tested the effect of NSAIDs on osteoblast (OB) differentiation and bone mineralization in primary bone-derived cells (BdCs) from mice, and in ankylosing spondylitis (AS) patients and human osteosarcoma cell line (SaOS2). Celecoxib significantly inhibited clinical arthritis and bone progression in the joints of SKGc, but not etoricoxib (another COX-2i), nor naproxen (COX-2 nonselective). Both DM-celecoxib, not inhibiting COX-2, and celecoxib, inhibited OB differentiation and bone mineralization in the BdCs of mice and AS patients, and in SaOS2, but etoricoxib or naproxen did not. The in silico study indicated that celecoxib and 2,5-dimethyl-celecoxib (DM-celecoxib) would bind to cadherin-11 (CDH11) with higher affinity than etoricoxib and naproxen. Celecoxib suppressed CDH11-mediated β-catenin signaling in the joints of SKGc, primary mice cells, and SaOS2 cells. Of the NSAIDs, only celecoxib inhibited bone progression in SKGc and OB differentiation and bone mineralization in the BdCs of mice and AS patients via CDH11/WNT signaling, independent of the COX-2 inhibition.