The present invention provides new protease resistant polypeptides which are variants of angiopoietin-like 3, as well as compositions and methods for treating, ameliorating or preventing conditions related to joint damage, including acute joint injury and arthritis. In a particular aspect, the present invention provides an isolated polypeptide comprising an amino acid sequence that has at least 95% amino acid sequence identity to an amino acid sequence selected from any one of SEQ ID Nos: 14-17, 19-22, 24-41 and 58-70, wherein the polypeptide comprises an amino acid that is a polar amino acid other than K or R at position 423, as determined with reference to SEQ ID NO:1, and wherein the polypeptide has chondrogenic activity.
