HtrA1 (high-temperature requirement protein A1) is a secreted multidomain protein with proven serine protease activity and the ability to regulate TGF-β (transforming growth factor-β)/BMP (bone morphogenetic protein) signalling. There is increasing evidence that HtrA1 regulates several pathological processes, including tumour development, Alzheimer's disease, age-related macular degeneration and osteoarthritis, although the mechanism(s) by which it regulates these processes have not been fully elucidated. Using overexpression and knock-down strategies, we have evidence demonstrating that HtrA1 is also a key regulator of physiological and pathological matrix mineralization in vitro. We propose that HtrA1 regulates mineralization by inhibiting TGF-β/BMP signalling and/or by cleaving specific matrix proteins, including decorin and MGP (matrix Gla protein). Taken together, these studies suggest that HtrA1 may be a novel therapeutic target for several diseases.
HtrA1: a novel regulator of physiological and pathological matrix mineralization?
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A.E. Canfield, K.D. Hadfield, C.F. Rock, E.C. Wylie, F.L. Wilkinson; HtrA1: a novel regulator of physiological and pathological matrix mineralization?. Biochem Soc Trans 1 August 2007; 35 (4): 669–671. doi: https://doi.org/10.1042/BST0350669
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