Calcium pentosan polysulfate is a multifaceted exosite inhibitor of aggrecanases

Troeberg L, Fushimi K, Khokha R, Emonard H, Ghosh P, Nagase H · FASEB Journal

Calcium PPS blocked the aggrecan-degrading activity of ADAMTS-4 and ADAMTS-5 at 10–40 nM by binding their non-catalytic domains, raised cartilage levels of the endogenous inhibitor TIMP-3 by blocking its endocytosis, and increased TIMP-3's affinity for the aggrecanases more than 100-fold.

Population

Recombinant aggrecanases and porcine cartilage explant cultures

Intervention

Calcium PPS at graded nanomolar concentrations

Comparator

Untreated enzyme and explant controls

Limitations

Enzyme and explant work only; Ghosh (PPS's developer) among the authors; tested the calcium salt rather than the sodium salt used clinically.