Schnurri-3 inhibition suppresses bone and joint damage in models of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to systemic and articular bone loss by activating bone resorption and suppressing bone formation. Despite current therapeutic agents, inflammation-induced bone loss in RA continues to be a significant clinical problem due to joint deformity and lack of articular and systemic bone repair. Here, we identify the suppressor of bone formation, Schnurri-3 (SHN3), as a potential target to prevent bone loss in RA.

A role for neutrophils in early enthesitis in spondyloarthritis.

Background: Neutrophils are present in the early phases of spondyloarthritis-related uveitis, skin and intestinal disease, but their role in enthesitis, a cardinal musculoskeletal lesion in spondyloarthritis, remains unknown. We considered the role of neutrophils in the experimental SKG mouse model of SpA and in human axial entheses.

Methods: Early inflammatory infiltrates in the axial and peripheral entheseal sites in SKG mice were evaluated using immunohistochemistry and laser capture microdissection of entheseal tissue.

Osteoblast-Osteoclast Communication and Bone Homeostasis.

Bone remodeling is tightly regulated by a cross-talk between bone-forming osteoblasts and bone-resorbing osteoclasts. Osteoblasts and osteoclasts communicate with each other to regulate cellular behavior, survival and differentiation through direct cell-to-cell contact or through secretory proteins. A direct interaction between osteoblasts and osteoclasts allows bidirectional transduction of activation signals through EFNB2-EPHB4, FASL-FAS or SEMA3A-NRP1, regulating differentiation and survival of osteoblasts or osteoclasts.

Bone Loss in Rheumatoid Arthritis: Basic Mechanisms and Clinical Implications.

Patients with rheumatoid arthritis (RA) have historically developed progressive damage of articular bone and cartilage, which correlates with disability over time. In addition, these patients are prone to periarticular and systemic bone loss, carrying additional morbidity. In contrast to what is seen in many other rheumatic diseases, the impact of inflammation on bone in RA is uniquely destructive.

Differential Effects of Inflammation on Bone and Response to Biologics in Rheumatoid Arthritis and Spondyloarthritis.

Purpose Of Review: We review the pathways, cytokines, and concepts important to the pathogenesis of bone resorption and formation in rheumatoid arthritis (RA) and spondyloarthritis (SpA).

Recent Findings: Research in bone biology has shed light on the pathogenesis of the joint destruction that occurs in RA and in peripheral SpA. However, understanding the mechanisms behind the bone formation seen in peripheral and axial SpA has been challenging.

Hepatic dysfunction is associated with vitamin D deficiency and poor glycemic control in diabetes mellitus.

Background/aims: The effect of the rising prevalence of nonalcoholic fatty liver disease on the 25-hydroxylation of pre-vitamin D in the liver, and consequent glycemic control in children with diabetes mellitus is not known. Our aim was to determine whether mild hepatic dysfunction was associated with impaired 25-hydroxylation of pre-vitamin D, and if this vitamin D deficiency was associated with impaired glycemic control in children and adolescents with type 1 diabetes (T1DM) and type 2 diabetes (T2DM).

Methods: We analyzed simultaneously measured HbA1c, ALT, AST, and 25OHD levels and clinical parameters in 121 children and adolescents with T1DM (n=81) and T2DM (n=40).