This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.
Our understating of the progression pathways in knee osteoarthritis (OA) has evolved dramatically in recent years, as described in a recent review article.1 Over the past 2 decades, we have come to view the knee joint as an organ unto itself (with cartilage, synovium, bone, ligaments, and capsule). In the knee, we add to the mix the meniscus, which not only guides motion but is responsible for weight distribution on articular cartilage. Investigations into the etiology and progression of knee OA have merged joint mechanics with insights from studies of inflammation and immunology.
Woodell-May and Sommerfeld examine the process of knee OA as a wound-healing response. Triggered by damage-associated molecular patterns, the innate immune system is typically the first responder to this process. The acute phase in wound healing is short and involves infiltration of neutrophils. In response to neutrophil signals, monocytes migrate from the vessels and differentiate into macrophages, initially type I (inflammatory), which help form the granulation tissue seen in wound healing.
One take-home from the review article is that OA progression may be driven by the chronic inflammation associated with continuing efforts to heal. The back-and-forth between stimulating inflammation (M1 macrophages) and modulating inflammation (M2 macrophages) seems to be predominately driven from the synovium. In addition, specific receptors and intracellular kinases (such as toll-like receptors and mitogen-activated protein kinase) are upregulated in many OA samples.
M1 macrophages promote the elaboration of TNFα and IL-1 by synovial cells. Both cytokines are also active in rheumatoid arthritis (RA). Biologic treatment directed at either one of those cytokines can be effective in RA, but such treatment does not appear to be effective in OA. Over the past decade, the use of autologous conditioned serum (serum drawn off after blood is exposed to glass beads and incubated) has been studied in an attempt to reduce IL-1 activity. The conditioned serum also seems to affect TNFα and has shown some early promise in OA cases.
This burgeoning basic-science knowledge about OA has the potential to lead to disease-modifying treatments, which would revolutionize how orthopaedists approach OA treatment.
Reference
1. Woodell-May JE, Sommerfeld SD. Role of Inflammation and the Immune System in the Progression of Osteoarthritis. J Orthop Res. 2020 Feb;38(2):253-257. doi: 10.1002/jor.24457. Epub 2019 Sep 12. Review. PMID: 31469192
