Autoimmunity and Bone
After completing his postdoctoral fellowship under the sponsorship of Dr. Firestein, Edward Schwarz, PhD, established his own musculoskeletal research lab at the University of Rochester Medical Center in upstate New York. Over the years, he and his team have studied a variety of musculoskeletal topics, from bone grafts, to bone resorption in psoriatic arthritis, to gene therapy, to the biochemistry of inflammation. This 2006 article focused on why patients with systemic lupus erythematosus (SLE) do not have erosive joint changes associated with their arthritis, whereas people with rheumatoid arthritis (RA) or psoriatic arthritis do.
What Problem Was Studied?
In people with RA or psoriatic arthritis, the disease leads to extensive joint damage that includes bone loss, cartilage degradation, and pannus tissue penetrating deep into cartilage and bone. In contrast, the arthritis associated with SLE does not involve erosive changes or aggressive invasion of synovial tissue into cartilage or bone.
Peripheral blood mononuclear cells (PBMC) travel to sites of inflammation where they differentiate into activated macrophages, dendritic cells or osteoclasts depending on the cytokines in the area. Dr. Schwarz and colleagues theorized that interferon-α, which is found in higher quantities in SLE than RA or psoriatic arthritis, biases myelopoiesis away from osteoclast and toward dendritic cell differentiation.
What Was Done in the Study?
To determine what cytokines are activating the PBMCs to form which types of cells, Dr. Schwarz ran a series of experiments on a mouse model of erosive arthritis.
What Were the Study Results?
They found that systemic interferon can, indeed, shift PBMC cell differentiation toward dendritic cells at the expense of osteoclast formation.
What Does This Mean to the Future of Bone Research?
Understanding the mechanisms behind bone remodeling and what factors can shift the balance between bone loss and bone growth can lead to treatments that can restore homeostasis. Restoring this balance could then prevent joint destruction in arthritis.