Screening method for therapeutic agent for chondropathy and modified chondrocyte for treatment of chondropathy

摘要

The use of salt-inducible kinase 3 allows screening for a substance having an effect of increasing cartilage volume and/or an effect of normalizing chondrocyte differentiation. A modified chondrocyte in which the expression or function of salt-inducible kinase 3 gene is inhibited or enhanced can be used to ameliorate a disease associated with reduced cartilage volume and/or a disease associated with impaired cartilage growth.

主权项

1. A screening method for a substance having an effect of increasing cartilage volume and/or an effect of reducing the speed of chondrocyte differentiation, the method comprising contacting (a1) a mammalian cell expressing endogenous salt-inducible kinase 3 SIK3, (b1) a cell into which a vector containing a reporter gene fused downstream of a mammalian SIK3 promoter has been introduced, or (c1) a mammalian SIK3 protein and its substrate, with a test substance, measuring (a2) the amount of SIK3 protein or mRNA in the mammalian cell, (b2) the promoter activity of mammalian SIK3 in the cell carrying the vector, (c2) the binding of the mammalian SIK3 protein to its substrate or (c2′) the phosphorylation of the substrate for the mammalian SIK3 protein, and selecting a test substance (a3) decreasing the amount of the SIK3 protein or mRNA, (b3) decreasing the promoter activity of SIK3, (c3) decreasing the binding of the SIK3 to its substrate, or (c3′) decreasing the phosphorylation of the substrate for SIK3, compared with a control group free from contact with the test substance.