MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation – divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation

Abstract

We found that inhibition of MAPK P38, P44/42 and Src family abrogated proteolytic cartilage degradation by blocking MMP synthesis and activity. However, only MAPK P44/42 was essential for aggrecanase-mediated aggrecan degradation. These data suggest that various aspects of cartilage degradation can be targeted independently by inhibiting specific upstream signaling pathway.

Activation of a7 Nicotinic Acetylcholine Receptors Prevents Monosodium Iodoacetate-Induced Osteoarthritis in Rats

“…The p38, Erk1/2 and JNK MAPKs signaling pathways are essential in cartilage depletion [30]. Sondergaard et al found that inhibition of the MAPK p38, p44/42 and Src family abolished proteolytic cartilage degradation by blocking MMP synthesis and activity [31]. Moreover, growing evidence demonstrates that NF-κB signaling as not only playing a key role in the pro-inflammatory stress-related responses of chondrocytes to extra- and intra-cellular insults, but also in the management of their differentiation program [32].…”

Mechanical injury of bovine cartilage explants induces depth-dependent, transient changes in MAP kinase activity associated with apoptosis

“…Cell signals amid stress-related responses are partially transmitted and communicated via the MAP kinases, and signalling through ERK, p38 and JNK have been implicated in early OA and models for mechanical stress of cartilage 1,15,32,33 including regulation of both chondrocyte gene expression and death 34,35 . Here, only p38 was activated above control levels early and most prominently in the superficial zone at the site of injury, followed by a significant drop in p38 activity in the superficial zone after 1 day.…”

Low-Intensity Pulsed Ultrasound Affects Chondrocyte Extracellular Matrix Production via an Integrin-Mediated p38 MAPK Signaling Pathway

“…The MAPK signaling pathway consists of extracellular signal-regulated kinase (ERK), p38 MAPK (p38) and cJun N-terminal kinase (JNK), all of which are constitutively expressed in most cell types, including chondrocytes (Karsdal et al 2008). The p38 MAPK signaling pathway mediates chondrocyte-perichondral communication (Stanton and Beier 2007), stabilizes chondrogenic transcription factor SOX 9 mRNA (Tew and Hardingham 2006) and is necessary for MMP expression and activity (Sondergaard et al 2010). Therefore, the p38 MAPK signaling pathway plays a major role in chondrocyte differentiation (Zhen et al 2001).…”