Lactoferrin Inhibits IL-1β-Induced Chondrocyte Apoptosis Through AKT1-Induced CREB1 Activation.
OBJECTIVE
Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA). Interleukin-1 beta (IL-1β) is widely used as a chondrocyte apoptosis-inducing agent, while lactoferrin (LF) is an anabolic reagent which has the potential to inhibit chondrocyte apoptosis. We assessed the effects of LF on cartilage degeneration in IL-1β-induced chondrocytes and in a rat model of OA, and explored the potential molecular mechanisms involved.


METHODS
Human articular chondrocytes (HACs) were treated with IL-1β alone or in combination with LF. MTT and flow cytometric assays were used to detect changes after treatment with LF. Western blotting was used to examine the relevant molecules regulating apoptosis.


RESULTS
We found that IL-1β reduced the viability of HACs, whereas 200 μg/mL of LF significantly counteracted the inhibitory effect of IL-1β. LF significantly inhibited IL-1β-induced HAC apoptosis. The protein expression of the apoptotic markers Caspase-3 and PARP was also significantly reduced in the LF treatment group when analyzed by western blotting. Furthermore, we found that LF triggered CREB1 phosphorylation in IL-1β-induced HAC apoptosis through AKT1 signaling. In addition, LF promoted the repair of articular cartilage damage in a rat OA model with elevated p-CREB levels.


CONCLUSIONS
These studies suggest that LF has an anti-apoptotic effect on IL-1β-induced chondrocytes, and thus may be a promising novel therapeutic agent for OA.
Department of Orthopaedics, Yangpu District Central Hospital, Tongji University School of Medicine, Shanghai, China.
Huaming
H
Xue
Yihui
Y
Tu
Tong
T
Ma
Xiaodong
X
Liu
Tao
T
Wen
Minwei
M
Cai
Zhidao
Z
Xia
Jiong
J
Mei
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002358:Cartilage, Articular / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D007781:Lactoferrin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D053583:Interleukin-1beta; C490098:LTF protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D007781:Lactoferrin