Monomeric C reactive protein (mCRP) regulates inflammatory responses in human and mouse chondrocytes

C-reactive protein (CRP) is an acute-phase protein that is used as an established biomarker to follow disease severity and progression in a plethora of inflammatory diseases. However, its pathophysiologic mechanisms of action are still poorly defined and remain elusive. CRP, in its pentameric form, exhibits weak anti-inflammatory activity. On the contrary, the monomeric isoform (mCRP) exhibits potent pro-inflammatory properties in endothelial cells, leukocytes, and platelets. So far, no data exists regarding mCRP effects in human or mouse chondrocytes. This work aimed to verify the pathophysiological relevance of mCRP in the etiology and/or progression of osteoarthritis (OA). We investigated the effects of mCRP in cultured human primary chondrocytes and in the chondrogenic ATDC5 mouse cell line. We determined mRNA and protein levels of relevant factors involved in inflammatory responses and the modulation of nitric oxide synthase type II (NOS2), an early inflammatory molecular target. We demonstrate, for the first time, that monomeric C reactive protein increases NOS2, COX2, MMP13, VCAM1, IL-6, IL-8, and LCN2 expression in human and murine chondrocytes. We also demonstrated that NF-kB is a key factor in the intracellular signaling of mCRP-driven induction of pro-inflammatory and catabolic mediators in chondrocytes. We concluded that mCRP exerts a sustained catabolic effect on human and murine chondrocytes, increasing the expression of inflammatory mediators and proteolytic enzymes, which can promote extracellular matrix (ECM) breakdown in healthy and OA cartilage. In addition, our results implicate the NF-kB signaling pathway in catabolic effects mediated by mCRP. In this article the authors demonstrate that monomeric C reactive protein (mCRP) increases NOS2, COX2, MMP13, VCAM1, IL-6, IL-8, and LCN2 expression in chondrocytes. mCRP exerts a sustained catabolic effect on chondrocytes, increasing the expression of inflammatory mediators and proteolytic enzymes, which can promote cartilage extracellular matrix breakdown and osteoarthritis development and progression.

Automated summary

This study demonstrates that monomeric C reactive protein (mCRP) exerts strong pro-inflammatory properties in chondrocytes, increasing the expression of various inflammatory mediators and proteolytic enzymes, thereby promoting breakdown of the extracellular matrix in cartilage.