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Expression of phosphocitrate-targeted genes in osteoarthritis menisci.

Sun Y, Mauerhan DR, Steuerwald NM, Ingram J, Kneisl JS, Hanley EN - Biomed Res Int (2014)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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Related in: MedlinePlus

Representative images of FGFR3 and SOX-9 immunostaining (magnification 10x). (a) FGFR3 immunostaining of normal menisci and OA menisci. (b) SOX-9 immunostaining of normal menisci and OA menisci.
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fig4: Representative images of FGFR3 and SOX-9 immunostaining (magnification 10x). (a) FGFR3 immunostaining of normal menisci and OA menisci. (b) SOX-9 immunostaining of normal menisci and OA menisci.

Mentions: Representative images of FGFR3 and SOX-9 immunostaining are provided in Figure 4. As shown in Figure 4(a), few FGFR3 immunostaining-positive cells were detected in the normal menisci and only a small number of FGFR3 immunostaining-positive cells were detected in the OA menisci. In contrast, strong SOX-9 immunostaining was detected in the normal menisci and the intensity of SOX-9 immunostaining and number of SOX-9 immunostaining-positive cells were decreased significantly in the OA menisci compared to the normal menisci (Figure 4(b)).


Expression of phosphocitrate-targeted genes in osteoarthritis menisci.

Sun Y, Mauerhan DR, Steuerwald NM, Ingram J, Kneisl JS, Hanley EN - Biomed Res Int (2014)

Representative images of FGFR3 and SOX-9 immunostaining (magnification 10x). (a) FGFR3 immunostaining of normal menisci and OA menisci. (b) SOX-9 immunostaining of normal menisci and OA menisci.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4265372&req=5

fig4: Representative images of FGFR3 and SOX-9 immunostaining (magnification 10x). (a) FGFR3 immunostaining of normal menisci and OA menisci. (b) SOX-9 immunostaining of normal menisci and OA menisci.
Mentions: Representative images of FGFR3 and SOX-9 immunostaining are provided in Figure 4. As shown in Figure 4(a), few FGFR3 immunostaining-positive cells were detected in the normal menisci and only a small number of FGFR3 immunostaining-positive cells were detected in the OA menisci. In contrast, strong SOX-9 immunostaining was detected in the normal menisci and the intensity of SOX-9 immunostaining and number of SOX-9 immunostaining-positive cells were decreased significantly in the OA menisci compared to the normal menisci (Figure 4(b)).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

Show MeSH
Related in: MedlinePlus