Related Experiment Video
Updated: Jun 19, 2026
Standardized Histomorphometric Evaluation of Osteoarthritis in a Surgical Mouse Model
Published on: May 6, 2020
Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis
Heiner Appel1, Gisela Ruiz-Heiland, Joachim Listing
1Charité Berlin, Campus Benjamin Franklin, Berlin, Germany.
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.
Insights
Osteocyte sclerostin expression is reduced in ankylosing spondylitis (AS), and low serum sclerostin levels correlate with spinal damage in AS patients. This suggests impaired osteocyte function in AS bone remodeling.
Area of Science:
- Bone Biology and Metabolism
- Rheumatology
- Osteocyte Function
Background:
- Osteocytes, bone cells within the mineralized matrix, are key regulators of bone mass and damage sensing.
- Sclerostin, an osteocyte-derived protein, inhibits bone formation and plays a role in bone remodeling.
- The specific role of osteocytes and sclerostin in the pathogenesis of ankylosing spondylitis (AS) remains unclear.
Purpose of the Study:
- To investigate the role of osteocytes in bone remodeling within the context of ankylosing spondylitis (AS).
- To assess sclerostin expression in osteocytes and serum levels in patients with AS compared to other arthritic conditions and healthy controls.
- To determine the correlation between serum sclerostin levels and radiographic progression in AS.
Main Methods:
- Immunohistochemistry was used to evaluate osteocyte sclerostin expression and death in joint tissues from patients with AS, rheumatoid arthritis (RA), osteoarthritis (OA), and controls.
- Serum sclerostin levels were measured using enzyme-linked immunosorbent assay (ELISA) in healthy individuals and AS patients.
- Longitudinal analysis correlated serum sclerostin levels with spinal radiographic progression in AS patients.
Main Results:
- Sclerostin expression was primarily localized to osteocytes.
- Osteocyte sclerostin expression was significantly reduced in osteoarthritis (OA) and virtually absent in ankylosing spondylitis (AS), unlike in healthy individuals and rheumatoid arthritis (RA) patients.
- Serum sclerostin levels were significantly lower in AS patients compared to healthy individuals, and lower levels were associated with increased syndesmophyte formation (new bone spurs) in the spine.
Conclusions:
- Osteocyte sclerostin expression is significantly impaired in patients with ankylosing spondylitis (AS), indicating a specific functional alteration in this disease.
- Reduced serum sclerostin levels in AS are linked to increased structural bone damage, highlighting sclerostin's role in suppressing bone formation.
- These findings underscore the importance of osteocyte-derived sclerostin in the bone remodeling abnormalities observed in AS.
