Abstract
In patients with osteoarthritis (OA), there is a decrease in both the concentration and molecular size of hyaluronan (HA) in the synovial fluid and cartilage. Cell migration-inducing hyaluronidase 1 (CEMIP), also known as hyaluronan (HA)-binding protein involved in HA depolymerization (HYBID), was recently reported as an HA depolymerization-related molecule expressed in the cartilage of patients with OA. However, the underlying mechanism of CEMIP regulation is not well understood. We found that CEMIP expression was transiently increased by interleukine-1β (IL-1β) stimulation in chondrocytic cells. We also observed that ERK activation and NF-κB nuclear translocation were involved in the induction of CEMIP by IL-1β. In addition, both administration of HA and mechanical strain attenuated the CEMIP induction in IL-1β-stimulated chondrocytes. In conclusion, we clarified the regulatory mechanism of CEMIP in chondrocytes by inflammatory cytokines and suggested the potential involvement in osteoarthritis development.
Highlights
The extracellular matrix of cartilage is composed mainly of hyaluronan (HA)–aggrecan network and type II collagens [1,2,3]
CEMIP-positive chondrocytes were located in the NITEGE-positive area of OA cartilage (c)
We examined the effect of mechanical strain on IL-1β-induced CEMIP expression in OUMS-27 cells
Summary
The extracellular matrix of cartilage is composed mainly of hyaluronan (HA)–aggrecan (a major cartilage proteoglycan) network and type II collagens [1,2,3]. HA is a major component of the synovial fluid (SF) and provides viscoelasticity retention, lubrication of joints, and cushioning against mechanical stress on articular cartilage [4]. Hyaluronic acid in articular cartilage has a high molecular weight (HMW; 1200 kDa) and density (~2.5–4 mg/mL) [5]. HMW HA-containing SF performs various functions such as cushioning, synovitis suppression, and elimination of reactive oxygen species [8]. Due to degradation and/or depolymerization, the SF of osteoarthritis (OA) patients contains HA at a lower concentration (1–2 mg/mL) with a lower molecular weight (2–2.5 kDa) than the SF in healthy subjects [9]. HA degradation and/or depolymerization are closely related with the onset of OA. InHthowisevsetur,dtyh,e wmeecehxaanmismineudndtehrleyiinngdtuhcetiroenguolaftiConEMof ICPEeMxIpPreesxspiroenssibony iinnflaartmhrmiticatcoarrytilacgyetokines, regulatrieomnaIionnfsthuCinsEcMlsetauIrdP. y,bwyeHexAamainnded mtheecihnadnuicctiaolnsotrf aCinE,MaIPndexpthreessuionndbeyrliynifnlagmminattroarcyelclyutolakrinseisg, naling mechanreisgmulsatiinonchoof nCdErMocIPytbicycHelAls.and mechanical strain, and the underlying intracellular signaling mechanisms in chondrocytic cells
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