Akademik Veri Yönetim Sistemi
EUROPEAN JOURNAL OF PEDIATRICS, cilt.184, sa.1, 2025 (SCI-Expanded)
Cystinosis metabolic bone disease (CMBD) is an emerging concept in infantile nephropathic cystinosis, patients presenting with bone pains, fractures, and deformations during teenage or early adulthood. The underlying mechanisms remain unclear. Our aim was to explore the pro-inflammatory profile of osteoclastic lineage in cystinotic patients. We obtained blood samples from 14 cystinotic patients and 10 pediatric healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated and used to explore by RT-qPCR the transcript expression of 8 inflammatory markers (Il-6, Il-8, Il-1 beta, CXCL1, CCL2/MCP-1, CXCR3, Il-1 Receptor, Il-6 Receptor). In addition, when possible, PBMCs were differentiated into osteoclasts for further experiments. The expression of Il-6, IL-8, CXCR3, and CCL2/MCP-1 was significantly increased in PBMCs from cystinotic patients. We also explored the expression of Il-1 Receptor and Il-6 Receptor, two major pro-osteoclastic signal inducers, in osteoclasts differentiated from PBMCs from controls (N = 3) and patients (N = 4). The expression of IL-1 Receptor (but not IL-6 receptor) was increased in osteoclasts obtained from cystinotic patients. Conclusion: There is an inflammatory profile in PBMCs and osteoclastic lineage in cells obtained from cystinotic patients. CXCR3 and MCP-1 stimulate migration and activation of macrophages, that may explain the previously reported local increased osteoclastogenesis. The osteoclastic overexpression of IL-1 Receptor is a relevant observation in the field since blocking Il-1 beta signaling has recently been proposed as a novel therapeutic approach to improve muscular wasting in this orphan disease.