Plain Language Summary
This research reveals that human leukocyte antigen-B27 (HLA-B27) misfolding activates pathways such as p-IRE1/sXBP1/RARB/TNAP within the enthesis (ligament and bone connective tissue) that lead to the development of syndesmophyte (bone) formation in ankylosing spondylitis mesenchymal stem cells (AS MSCs). Targeting these pathways helps identify strategies to block unfavorable bone formation. The dual effect of pamidronate, which blocks mineralization and inhibits bony placement, could potentially be used in drug therapies to prevent spinal fusion and osteoporosis. A novel animal-based model that mimics the bony placement developed in this research is suggested as a more suitable platform for future drug testing. Furthermore, it is proven that serum BAP levels are potential biomarkers for the identification of high-risk AS patients predisposed to radiography progression, and TNAP inhibitors could be utilized in bony outgrowth prevention.
Ankylosing spondylitis (AS) is an inflammatory disease that causes the fusion of small bones in the spine resulting in a forward-hunched posture. The association of the development of AS ties closely with HLA-B27. Treatment options available currently treat inflammation but do not entirely stop unfavorable bone formation. Factors such as minimal understanding of stromal activation, limited access to drug screening, and unavailability of biomarkers to identify high-risk patients are reasons for the limited treatment options available in the market. Mesenchymal stem cells (MSCs) isolated from the connective tissues of ligaments and bones of AS patients reveal a pathway relevant to the syndesmophyte growth in AS patients, which could be explored to determine drug treatment options. In a clinical setting, by working on the serum from AS patients, this study explores the possibility of utilizing serum TNAP levels as a biomarker to identify high-risk patients. Findings of the research show HLA-B27 as a mediator of AS, opening up new strategies to further develop novel and effective AS therapy.
The SDG Impact
According to data published in BMC Rheumatology, the prevalence rate for AS doubled from the year 2006 to 2016. Its prevalence is higher among men compared to women and is said to show signs and symptoms during early adulthood. The progression of this illness clearly poses a threat to presume a normal lifestyle, especially concerning employment and mobility. The establishment of the role of HLA-B27 associated with ankylosing spondylitis aligns with Goal 3: Good health and well-being of Sustainable Development Goals. By studying the genome-wide association, more effective treatments and prevention methods could be developed through bioengineering, ultimately improving the quality of life of those suffering from AS.