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Updated: Apr 19, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Expression of phosphocitrate-targeted genes in osteoarthritis menisci
Yubo Sun1, David R Mauerhan1, Nury M Steuerwald2
1Department of Orthopedic Surgery, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC 28232, USA.
Abstract:
Phosphocitrate (PC) inhibited calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the molecular mechanisms remain elusive. This study sought to determine PC targeted genes and the expression of select PC targeted genes in OA menisci to test hypothesis that PC exerts its disease modifying activity in part by reversing abnormal expressions of genes involved in OA. We found that PC downregulated the expression of numerous genes classified in immune response, inflammatory response, and angiogenesis, including chemokine (C-C motif) ligand 5, Fc fragment of IgG, low affinity IIIb receptor (FCGR3B), and leukocyte immunoglobulin-like receptor, subfamily B member 3 (LILRB3). In contrast, PC upregulated the expression of many genes classified in skeletal development, including collagen type II alpha1, fibroblast growth factor receptor 3 (FGFR3), and SRY- (sex determining region Y-) box 9 (SOX-9). Immunohistochemical examinations revealed higher levels of FCGR3B and LILRB3 and lower level of SOX-9 in OA menisci. These findings indicate that OA is a disease associated with immune system activation and decreased expression of SOX-9 gene in OA menisci. PC exerts its disease modifying activity on OA, at least in part, by targeting immune system activation and the production of extracellular matrix and selecting chondroprotective proteins.
Insights
Phosphocitrate (PC) reduces osteoarthritis (OA) by targeting immune responses and promoting skeletal development genes. This study reveals PC
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Osteoarthritis (OA) is a degenerative joint disease with complex molecular underpinnings.
- Calcium crystal deposition is implicated in OA pathogenesis.
- The molecular mechanisms by which phosphocitrate (PC) exerts its protective effects in OA are not fully understood.
Purpose of the Study:
- To identify genes targeted by PC in the context of osteoarthritis.
- To investigate the expression of PC-targeted genes in OA menisci.
- To test the hypothesis that PC modifies OA by reversing abnormal gene expression.
Main Methods:
- Gene expression analysis in guinea pig models and human OA menisci.
- Identification of PC-modulated genes.
- Immunohistochemical analysis of specific protein markers (FCGR3B, LILRB3, SOX-9) in OA menisci.
Main Results:
- PC downregulated genes involved in immune response, inflammation, and angiogenesis (e.g., chemokine (C-C motif) ligand 5, FCGR3B, LILRB3).
- PC upregulated genes associated with skeletal development (e.g., collagen type II alpha1, FGFR3, SOX-9).
- OA menisci showed elevated FCGR3B and LILRB3 levels and reduced SOX-9 expression compared to controls.
Conclusions:
- Osteoarthritis is characterized by immune system activation and decreased SOX-9 expression in menisci.
- PC demonstrates disease-modifying activity in OA, partly by modulating immune responses and extracellular matrix production.
- PC's therapeutic potential lies in its ability to target immune activation and promote chondroprotective gene expression.
