As musculoskeletal diseases become an emerging healthcare problem worldwide, profound and comprehensive research has been focused on the biochemistry of bone metabolism in the past decades. Wnt signalling, one of the novel described pathways influencing bone metabolism from the early stages of tissue development, has been recently in the centre of attention. Several Wnt ligands are implied in bone forming pathways via canonical (β-catenin dependent) and non-canonical (β-catenin independent) signalling. Osteoporosis, a catabolic bone disease, has its pathologic background related, inter alia, to alterations in the Wnt signalling, thus key modulators of these pathways became one of the most promising targets in the treatment of osteoporosis. Antibodies inhibiting the activity of endogenous Wnt pathway inhibitors (sclerostin, dickkopf) are recently under clinical trials. The current article offers a brief review of the Wnt signalling pathways, its implication in bone metabolism and fate, and the therapeutic possibilities of osteoporosis through Wnt signalling.
Objectives: Study of circulating and synovial levels of osteocalcin, osteoprotegerin and tumor necrosis factor-alpha (TNF-α) in patients with different stages of knee osteoarthritis and correlation analysis of these parameters with disease severity.
Methods: We enrolled 20 patients with different stages of knee osteoarthritis. The IKDC score (International Knee Documentation Comittee, 2000) was determined for each patient. Based on these data patients were divided into two groups: group I (advanced osteoarthritis) and group II (early osteoarthritis). Serum and synovial fluid levels of osteocalcin, osteoprotegerin, TNF-α were determined.
Results: For the entire group the level of osteocalcin in the serum showed higher values than in the synovial fluid. We found statistically significant differences in the serum levels of osteocalcin between the two groups (group I: 2.18 ± 0.54 ng/ml, group II: 6.07 ± 1.98 ng/ml, p = 0.019). Serum and synovial osteocalcin in the whole study lot could not be correlated with the disease score, however we observed a tendency towards significant negative correlation between the serum osteocalcin and IKDC score for group I and between synovial osteocalcin and IKDC score in group II. In the entire group, synovial osteoprotegerin concentration was six times higher than the serum osteoprotegerin level (p <0.0001) and TNF-α showed higher circulating levels than local concentrations.
Conclusions: In the advanced osteoarthritis group the serum and synovial osteocalcin show lower values than in the early osteoarthritis group, which means that as the disease progresses, bone anabolism decreases. In the case of osteoprotegerin, no significant difference between the two groups was detected.