Reading this paper (1) carefully, we do not find that “S100A4 regulates IL-1β-dependent induction of MMP-13,” as stated in the title, is convincingly demonstrated. Thorough interpretation of the data raises several compelling concerns, and we doubt conclusions drawn based on comments specified below.
The authors state that “the immunofluorescence data (Fig. 1A) showed that under basal conditions S100A4 was predominantly localized in the cytoplasm.” We agree that the red channel (middle row, Fig. 1A) shows S100A4 at all time points, and in Fig. 1B cytoplasmic staining is equally strong at all time points. Therefore, why is cytoplasmic staining of S100A4 absent at time 0 and 120 min in the overlay image?
In Fig. 2B, why does the SUMO antibody pick up S100A4 that is not SUMOylated, and could the claimed SUMO-S100A4 be instead a multimeric form of SUMO?
For clarification, basal levels of endogenous and extracellular S100A4 in chondrocytes should be included in Figs. 3B and 4C, respectively.
In our opinion, Fig. 4, A and B, lacks the IL-1β-treated pEGFP empty vector-transfected control. This is, however, included in Fig. 4D and gives an ∼2.25-fold increase in MMP-13 mRNA. When transferring these data into Fig. 4B and comparing it to the ∼2.75-fold increase induced by overexpressed S100A4, a significant difference is not evident. Moreover, in Fig. 4D, no p value or comment is given on the effect of IL-1β treatment alone (bar 1 versus 4) compared to overexpressed S100A4-GFP (bar 2 versus 5).
Why does the effect of IL-1β on S100A4-GFP-transfected cells change from ∼2.75-fold in Fig. 4A (bar 2) to ∼4-fold in Fig. 4B (bar 5)?
References
- 1.Miranda K. J., Loeser R. F., Yammani R. R. (2010) J. Biol. Chem. 285, 31517–31524 [DOI] [PMC free article] [PubMed] [Google Scholar]