Impact of inflammation on the osteoblast in rheumatic diseases

Abstract

Normal bone remodeling depends upon a balance between the action of bone-resorbing cells, osteoclasts, and bone-forming cells, osteoblasts. When this balance is disrupted, as is seen in inflammatory diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS), abnormal bone loss or bone formation occurs. In RA, proinflammatory cytokines induce osteoclast differentiation and inhibit osteoblast maturation, leading to articular bone erosions. In contrast, the inflammatory milieu in AS leads to excessive osteoblast activation and bone formation at sites of entheses. While much information exists about the effects of proinflammatory cytokines on osteoclast differentiation and function, more recent studies have begun to elucidate the impact of inflammation on the osteoblast. This review will summarize the mechanisms by which inflammation perturbs bone homeostasis, with a specific focus on the osteoblast.

Figure 1

Comparison of bone pathologies in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). A) RA. Histologic section of the talus bone in the ankle joint from the K/BxN serum transfer arthritis mouse model, showing pannus eroding into bone and entering the marrow space (star). Schematic of an inflamed RA joint is shown below, demonstrating that bone erosions occur at sites of pannus invasion into bone and the bone marrow space. B) AS. Histologic section from an inflammatory mouse model showing periosteal new bone formation (NB, star), surrounded by inflammatory cells and adjacent to the insertion site of a large tendon (T, arrow). The schematic below depicts the site of new bone formation in AS, at areas of tendon/ligament insertion into bone. Code: pannus (P), erosion site (E), cortical bone (CB), bone marrow (BM), tendon (T), enthesial inflammation (EI), periosteal new bone (NB).