When searching for protease targets, appropriate controls are needed (i.e. healthy or non-digested tissues) in order to avoid reporting artefactual cleavages that may arise from experimental processing, or identifying those that are part of normal physiological turnover. Moreover, the addition of broad-spectrum protease inhibitors during extraction reduces the chance of producing artefactual fragmentation. More sophisticated methods include free C- or N-terminal labelling of endogenous protease-generated fragments prior to digestion for MS analysis.101 For example, the TAILS proteomics approach (isotope-based N-terminal labelling) has been successfully applied by Prudova et al.102 to analyse the degradome of MMP-2 and MMP-9. The same authors used a similar methodology to characterize the degradation of proteolytic fragments in human platelets.103 Ultimately, after identification of cleavage sites, targeted proteomics can be used to study the abundance of ECM fragments in clinical samples.