Limits...
Acidic pH environment induces autophagy in osteoblasts

View Article: PubMed Central - PubMed

ABSTRACT

Osteoblasts (OBs) play an important role in bone fracture healing, yet the extreme adverse microenvironment in fracture sites has a negative impact on the survival of OBs. Therefore, it is important to study how OBs behave in the complex fracture microenvironment. Studies have shown that autophagy plays a pivotal role in maintaining cellular homeostasis and defending the cell against adverse microenvironments. In this study we found the induction of autophagy in OBs at femoral bone fracture sites, which may be a result of ischemia, oxidative stress and hypoxia within the local area. At fracture sites a low pH environment also developed. Until now it has been unclear whether the induction of autophagy in osteoblasts is triggered by the acidic pH environment. Therefore, we cultured OBs in vitro in media of different pH values, and found both autophagy and apoptosis increased in OBs in acidic conditions. However, when autophagy inhibitor chloroquine (CQ) was used, apoptosis increased significantly compared with that without CQ. Thus indicating that inhibition of autophagy may promote apoptosis in OBs in an acidic environment, which may provide a new therapeutic strategy to decrease cell apoptosis in OBs through the use of drugs that modulate the autophagic state.

No MeSH data available.


Related in: MedlinePlus

Suppression of autophagy promotes apoptosis in OBs.(A) Cell apoptosis increased in media with CQ with the decrease of pH value at the time of 24 h. (B) Cell apoptosis rate with 6.4 + CQ, 6.8 + CQ and 7.4 + CQ for 24 h. *P < 0.05 vs. pH 6.8 + CQ(or pH 7.4 + CQ). (C) Moreover, the rate of apoptosis in OBs with CQ is higher than that without CQ. Values are the mean ± sd, *P < 0.05 in comparison to the control by one-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5382697&req=5

f4: Suppression of autophagy promotes apoptosis in OBs.(A) Cell apoptosis increased in media with CQ with the decrease of pH value at the time of 24 h. (B) Cell apoptosis rate with 6.4 + CQ, 6.8 + CQ and 7.4 + CQ for 24 h. *P < 0.05 vs. pH 6.8 + CQ(or pH 7.4 + CQ). (C) Moreover, the rate of apoptosis in OBs with CQ is higher than that without CQ. Values are the mean ± sd, *P < 0.05 in comparison to the control by one-way ANOVA.

Mentions: In order to study the relationship between apoptosis and autophagy, MC3T3-E1 cells were exposed to autophagy inhibitor CQ. The rate of cellular apoptosis increased when cells were treated with CQ in parallel with exposure to acidic conditions (Fig. 4A,B). Moreover, a larger proportion of apoptotic cells were observed when the cells were treated with CQ at all three experimental pH levels (7.4,6.8 and 6.4) (Fig. 4C).


Acidic pH environment induces autophagy in osteoblasts
Suppression of autophagy promotes apoptosis in OBs.(A) Cell apoptosis increased in media with CQ with the decrease of pH value at the time of 24 h. (B) Cell apoptosis rate with 6.4 + CQ, 6.8 + CQ and 7.4 + CQ for 24 h. *P < 0.05 vs. pH 6.8 + CQ(or pH 7.4 + CQ). (C) Moreover, the rate of apoptosis in OBs with CQ is higher than that without CQ. Values are the mean ± sd, *P < 0.05 in comparison to the control by one-way ANOVA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382697&req=5

f4: Suppression of autophagy promotes apoptosis in OBs.(A) Cell apoptosis increased in media with CQ with the decrease of pH value at the time of 24 h. (B) Cell apoptosis rate with 6.4 + CQ, 6.8 + CQ and 7.4 + CQ for 24 h. *P < 0.05 vs. pH 6.8 + CQ(or pH 7.4 + CQ). (C) Moreover, the rate of apoptosis in OBs with CQ is higher than that without CQ. Values are the mean ± sd, *P < 0.05 in comparison to the control by one-way ANOVA.
Mentions: In order to study the relationship between apoptosis and autophagy, MC3T3-E1 cells were exposed to autophagy inhibitor CQ. The rate of cellular apoptosis increased when cells were treated with CQ in parallel with exposure to acidic conditions (Fig. 4A,B). Moreover, a larger proportion of apoptotic cells were observed when the cells were treated with CQ at all three experimental pH levels (7.4,6.8 and 6.4) (Fig. 4C).

View Article: PubMed Central - PubMed

ABSTRACT

Osteoblasts (OBs) play an important role in bone fracture healing, yet the extreme adverse microenvironment in fracture sites has a negative impact on the survival of OBs. Therefore, it is important to study how OBs behave in the complex fracture microenvironment. Studies have shown that autophagy plays a pivotal role in maintaining cellular homeostasis and defending the cell against adverse microenvironments. In this study we found the induction of autophagy in OBs at femoral bone fracture sites, which may be a result of ischemia, oxidative stress and hypoxia within the local area. At fracture sites a low pH environment also developed. Until now it has been unclear whether the induction of autophagy in osteoblasts is triggered by the acidic pH environment. Therefore, we cultured OBs in vitro in media of different pH values, and found both autophagy and apoptosis increased in OBs in acidic conditions. However, when autophagy inhibitor chloroquine (CQ) was used, apoptosis increased significantly compared with that without CQ. Thus indicating that inhibition of autophagy may promote apoptosis in OBs in an acidic environment, which may provide a new therapeutic strategy to decrease cell apoptosis in OBs through the use of drugs that modulate the autophagic state.

No MeSH data available.


Related in: MedlinePlus