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Do Matrix Metalloproteases and Tissue Inhibitors of Metalloproteases in Tenocytes of the Rotator Cuff Differ with Varying Donor Characteristics?

Klatte-Schulz F, Aleyt T, Pauly S, Geißler S, Gerhardt C, Scheibel M, Wildemann B - Int J Mol Sci (2015)

Bottom Line: Furthermore, the expression and secretion of TIMP-1, -2 and -3 was enhanced with age, muscle fatty infiltration and tear size.The interaction between MMPs and TIMPs is a complex process, since TIMPs are not only inhibitors, but also activators of MMPs.This study shows that MMPs and TIMPs might play an important role in degenerative tendon pathologies.

View Article: PubMed Central - PubMed

Affiliation: Julius Wolff Institute, Center for Musculoskeletal Surgery, Charité-Universitaetsmedizin Berlin, 13353 Berlin, Germany. franka.klatte@charite.de.

ABSTRACT
An imbalance between matrix metalloproteases (MMPs) and the tissue inhibitors of metalloproteases (TIMPs) may have a negative impact on the healing of rotator cuff tears. The aim of the project was to assess a possible relationship between clinical and radiographic characteristics of patients such as the age, sex, as well as the degenerative status of the tendon and the MMPs and TIMPs in their tenocyte-like cells (TLCs). TLCs were isolated from ruptured supraspinatus tendons and quantitative Real-Time PCR and ELISA was performed to analyze the expression and secretion of MMPs and TIMPs. In the present study, MMPs, mostly gelatinases and collagenases such as MMP-2, -9 and -13 showed an increased expression and protein secretion in TLCs of donors with higher age or degenerative status of the tendon. Furthermore, the expression and secretion of TIMP-1, -2 and -3 was enhanced with age, muscle fatty infiltration and tear size. The interaction between MMPs and TIMPs is a complex process, since TIMPs are not only inhibitors, but also activators of MMPs. This study shows that MMPs and TIMPs might play an important role in degenerative tendon pathologies.

No MeSH data available.


Related in: MedlinePlus

MMPs and TIMPs grouped according to the age of the donors (under 65 years (n = 16) and over 65 years (n = 14)). (A) qRT-PCR was performed to analyze gene expression. The box plot data represent the relative gene expression with 18S as reference gene using the ΔCt method with efficiency correction. The mRNA levels of MMP-2, -9, -13 and TIMP-2, -3 are significantly increased with higher age; (B) Protein levels were analyzed using ELISA and normalized to total protein content (Coomassie Plus assay). Protein levels of MMP-2 and TIMP-1 were significantly elevated with higher age. To allow visualization of all MMPs/TIMPs in one figure, MMP-9 and -13 values were multiplied by 105.
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ijms-16-13141-f003: MMPs and TIMPs grouped according to the age of the donors (under 65 years (n = 16) and over 65 years (n = 14)). (A) qRT-PCR was performed to analyze gene expression. The box plot data represent the relative gene expression with 18S as reference gene using the ΔCt method with efficiency correction. The mRNA levels of MMP-2, -9, -13 and TIMP-2, -3 are significantly increased with higher age; (B) Protein levels were analyzed using ELISA and normalized to total protein content (Coomassie Plus assay). Protein levels of MMP-2 and TIMP-1 were significantly elevated with higher age. To allow visualization of all MMPs/TIMPs in one figure, MMP-9 and -13 values were multiplied by 105.

Mentions: To determine the influence of donor age, donors were segregated into two groups: under 65 years (n = 16) and over 65 years (n = 14). The analysis revealed an age-dependent increase in the mRNA-expression levels of MMP-2, -9, -13 and TIMP-2, -3 (Figure 3A). This could only be confirmed at the protein level for MMP-2. In addition, protein levels of TIMP-1 were significantly elevated in TLCs from older donors, while mRNA expression was unaltered (Figure 3B). Spearman’s rho correlation revealed mild correlations between the age and the mRNA levels of MMP-2 (Spearman’s rank correlation coefficient (rs) = 0.504; p = 0.005), TIMP-2 (rs = 0.485; p = 0.007), and TIMP-3 (rs = 0.455; p = 0.012) (Table 1).


Do Matrix Metalloproteases and Tissue Inhibitors of Metalloproteases in Tenocytes of the Rotator Cuff Differ with Varying Donor Characteristics?

Klatte-Schulz F, Aleyt T, Pauly S, Geißler S, Gerhardt C, Scheibel M, Wildemann B - Int J Mol Sci (2015)

MMPs and TIMPs grouped according to the age of the donors (under 65 years (n = 16) and over 65 years (n = 14)). (A) qRT-PCR was performed to analyze gene expression. The box plot data represent the relative gene expression with 18S as reference gene using the ΔCt method with efficiency correction. The mRNA levels of MMP-2, -9, -13 and TIMP-2, -3 are significantly increased with higher age; (B) Protein levels were analyzed using ELISA and normalized to total protein content (Coomassie Plus assay). Protein levels of MMP-2 and TIMP-1 were significantly elevated with higher age. To allow visualization of all MMPs/TIMPs in one figure, MMP-9 and -13 values were multiplied by 105.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490489&req=5

ijms-16-13141-f003: MMPs and TIMPs grouped according to the age of the donors (under 65 years (n = 16) and over 65 years (n = 14)). (A) qRT-PCR was performed to analyze gene expression. The box plot data represent the relative gene expression with 18S as reference gene using the ΔCt method with efficiency correction. The mRNA levels of MMP-2, -9, -13 and TIMP-2, -3 are significantly increased with higher age; (B) Protein levels were analyzed using ELISA and normalized to total protein content (Coomassie Plus assay). Protein levels of MMP-2 and TIMP-1 were significantly elevated with higher age. To allow visualization of all MMPs/TIMPs in one figure, MMP-9 and -13 values were multiplied by 105.
Mentions: To determine the influence of donor age, donors were segregated into two groups: under 65 years (n = 16) and over 65 years (n = 14). The analysis revealed an age-dependent increase in the mRNA-expression levels of MMP-2, -9, -13 and TIMP-2, -3 (Figure 3A). This could only be confirmed at the protein level for MMP-2. In addition, protein levels of TIMP-1 were significantly elevated in TLCs from older donors, while mRNA expression was unaltered (Figure 3B). Spearman’s rho correlation revealed mild correlations between the age and the mRNA levels of MMP-2 (Spearman’s rank correlation coefficient (rs) = 0.504; p = 0.005), TIMP-2 (rs = 0.485; p = 0.007), and TIMP-3 (rs = 0.455; p = 0.012) (Table 1).

Bottom Line: Furthermore, the expression and secretion of TIMP-1, -2 and -3 was enhanced with age, muscle fatty infiltration and tear size.The interaction between MMPs and TIMPs is a complex process, since TIMPs are not only inhibitors, but also activators of MMPs.This study shows that MMPs and TIMPs might play an important role in degenerative tendon pathologies.

View Article: PubMed Central - PubMed

Affiliation: Julius Wolff Institute, Center for Musculoskeletal Surgery, Charité-Universitaetsmedizin Berlin, 13353 Berlin, Germany. franka.klatte@charite.de.

ABSTRACT
An imbalance between matrix metalloproteases (MMPs) and the tissue inhibitors of metalloproteases (TIMPs) may have a negative impact on the healing of rotator cuff tears. The aim of the project was to assess a possible relationship between clinical and radiographic characteristics of patients such as the age, sex, as well as the degenerative status of the tendon and the MMPs and TIMPs in their tenocyte-like cells (TLCs). TLCs were isolated from ruptured supraspinatus tendons and quantitative Real-Time PCR and ELISA was performed to analyze the expression and secretion of MMPs and TIMPs. In the present study, MMPs, mostly gelatinases and collagenases such as MMP-2, -9 and -13 showed an increased expression and protein secretion in TLCs of donors with higher age or degenerative status of the tendon. Furthermore, the expression and secretion of TIMP-1, -2 and -3 was enhanced with age, muscle fatty infiltration and tear size. The interaction between MMPs and TIMPs is a complex process, since TIMPs are not only inhibitors, but also activators of MMPs. This study shows that MMPs and TIMPs might play an important role in degenerative tendon pathologies.

No MeSH data available.


Related in: MedlinePlus