Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis

Abstract

Objective. Osteocytes are considered to be sensors of bone damage and regulators of bone mass by specifically expressing sclerostin, an inhibitor of bone formation. The contribution of osteocytes in regulating local bone remodeling in arthritis is unknown. The aim of this study was to investigate the role of osteocytes as contributors to bone remodeling in ankylosing spondylitis (AS).Methods. Sclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, patients with rheumatoid arthritis (RA), and patients with osteoarthritis (OA), as well as from control subjects. In addition, the serum level of sclerostin was assessed by enzyme-linked immunosorbent assay in healthy subjects and patients with AS; this assessment included the longitudinal correlation of sclerostin serum levels and radiographic progression in the spine of patients with AS.Results. Sclerostin expression was confined exclusively to osteocytes. Whereas the majority of osteocytes in healthy individuals and patients with RA were sclerostin positive, expression was significantly reduced in patients with OA and was virtually absent in patients with AS. Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Importantly, low serum sclerostin levels in patients with AS were significantly associated with the formation of new syndesmophytes (P ‫؍‬ 0.007).Conclusion. Sclerostin expression is impaired in patients with AS, suggesting a specific alteration of osteocyte function in this disease. A low serum level of sclerostin in the setting of AS is linked to increased structural damage, emphasizing the role of sclerostin in the suppression of bone formation.Ankylosing spondylitis (AS) is an inflammatory disease that predominantly affects axial joints and intervertebral spaces. AS is characterized by tight interplay between chronic inflammation and bone formation (1), which is only partly understood. Local inflammation appears to be crucial for bony proliferations along periosteal and entheseal sites (1). Inflammatory lesions are typically located in the subchondral bone marrow (2-4) and are preferentially seen at sites that later develop bony proliferations and ankylosis (3,4), suggesting a link between inflammation and bone formation.These observations, which suggest a functional link between inflammatory lesions inside the cortical bone barrier and bony proliferations outside this barrier, indicate that there is certain kind of "communication"Drs.

GP130 cytokines and bone remodelling in health and disease

“…OSM also induces proteoglycan loss and cartilage damage ex-vivo (97,100). Interestingly, decreased sclerostin expression was observed in bone from OA patients compared to normal or RA patients (91). Given that OSM can downregulate sclerostin expression in osteocytes (43) and promote bone formation, it is possible that OSM may function in this manner in OA to induce osteophyte formation and/or subchondral bone formation.…”

“…Recently downregulation of the Wnt signalling antagonist sclerostin in osteocytes has been noted at sites adjacent to syndesmophyte formation in retrieved tissues from ankylosing spondylitis patients (91) suggesting that this may be one mechanism by which bone formation is induced in the context of inflammation and mechanical strain at the entheseal site.…”

Sclerostin: A gem from the genome leads to bone-building antibodies

“…(84) Conversely, in ankylosing spondylitis, a disease characterized by inflammation-associated bony proliferations, local sclerostin production appears to be downregulated. (85) In mice, oncostatin M, a cytokine expressed by osteoblasts, osteocytes, and activated T cells, has been found to downregulate sclerostin expression by signaling through the leukemia inhibitory factor receptor (LIFR)-gp130 receptor complex. (86) In a mouse model of chronic colitis, short-term treatment with Scl-Ab had no anti-inflammatory effects but increased bone formation and reversed both inflammationinduced bone loss and the inflammation-induced decline in bone mechanical properties.…”

Updating the OMERACT Filter: Implications for Imaging and Soluble Biomarkers

“…], for example, MMP3 is significantly associated with this endpoint and it is now under further evaluation 54,55,56,57,58 . Among imaging techniques, ultrasound was considered an interesting candidate for assessing SpA enthesitis as a marker of inflammatory activity both at site specific (entheses) and patient levels 59,60,61,62,63 .…”