Riyadh Military Hospital

About: Riyadh Military Hospital is a healthcare organization based out in Riyadh, Saudi Arabia. It is known for research contribution in the topics: Population & Hepatitis C. The organization has 364 authors who have published 301 publications receiving 7223 citations. The organization is also known as: Prince Sultan Military Medical City & RMH.

Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation

Abstract: Fibroblast growth factor (FGF) 23 inhibits renal phosphate reabsorption by activating FGF receptor (FGFR) 1c in a Klotho-dependent fashion. The phosphaturic activity of FGF23 is abrogated by proteolytic cleavage at the RXXR motif that lies at the boundary between the FGF core homology domain and the 72-residue-long C-terminal tail of FGF23. Here, we show that the soluble ectodomains of FGFR1c and Klotho are sufficient to form a ternary complex with FGF23 in vitro. The C-terminal tail of FGF23 mediates binding of FGF23 to a de novo site generated at the composite FGFR1c-Klotho interface. Consistent with this finding, the isolated 72-residue-long C-terminal tail of FGF23 impairs FGF23 signaling by competing with full-length ligand for binding to the binary FGFR-Klotho complex. Injection of the FGF23 C-terminal tail peptide into healthy rats inhibits renal phosphate excretion and induces hyperphosphatemia. In a mouse model of renal phosphate wasting attributable to high FGF23, the FGF23 C-terminal peptide reduces phosphate excretion, leading to an increase in serum phosphate concentration. Our data indicate that proteolytic cleavage at the RXXR motif abrogates FGF23 activity by a dual mechanism: by removing the binding site for the binary FGFR-Klotho complex that resides in the C-terminal region of FGF23, and by generating an endogenous inhibitor of FGF23. We propose that peptides derived from the C-terminal tail of FGF23 or peptidomimetics and small-molecule organomimetics of the C-terminal tail can be used as therapeutics to treat renal phosphate wasting.

Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus

Abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that causes substantial morbidity As is typical for many other multifactorial disorders, much of the heritability of SLE remains unknown We identified a rare autosomal recessive form of SLE, in which autozygome analysis revealed a null mutation in the DNASE1L3 gene The DNASE1L3-related SLE we describe was always pediatric in onset and correlated with a high frequency of lupus nephritis Our findings confirm the critical role of impaired clearance of degraded DNA in SLE pathogenesis

CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Abstract: Altered growth and function of synoviocytes, the intimal cells which line joint cavities and tendon sheaths, occur in a number of skeletal diseases. Hyperplasia of synoviocytes is found in both rheumatoid arthritis and osteoarthritis, despite differences in the underlying aetiologies of the two disorders. We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome. Using a positional-candidate approach, we identified mutations in a gene (CACP) encoding a secreted proteoglycan as the cause of CACP. The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins. In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium. The similarity of CACP sequence to that of other protein families and the expression of CACP in non-skeletal tissues suggest it may have diverse biological activities.

Meta-Analysis of Navigation vs Conventional Total Knee Arthroplasty

Abstract: Navigated total knee arthroplasty (TKA) is promoted as a means to improve limb and prosthesis alignment. This study involved a systematic review and meta-analysis for all randomized controlled trials in the literature from 1986 to 2009 comparing alignment outcomes between navigated and conventional TKA. Alignment outcomes were pooled using a random-effects model, and heterogeneity was explored. Twenty-three randomized controlled trials were identified comparing navigated vs conventional TKA involving 2541 patients. Patients who underwent navigated TKA had a significantly lower risk of implant malalignment at more than 3° as well as more than 2°. In addition, the risk of malalignment was reduced for the coronal plane tibial and femoral components as well as femoral and tibial slope. This meta-analysis demonstrates that navigated TKA provides significant improvement in prosthesis alignment.