Patent ID: 7232796

Claim:
A method of stimulating osteoblasts after bone fracture or surgical intervention comprising administering an effective amount of a stimulating agent in combination with a graft to a patient in need thereof, wherein the stimulating agent is a) tissue inhibitor of metalloproteinases-2 (TIMP-2) having the amino acid sequence Z 1 CSCSPVHPQQAFCNADVVIRAKAVSEKEVDSGNDIYGNPIKRIQYEI KQIKMFKGP(residues 1–56 of SEQ ID NO:1) X1KDIEFIYTAPSSAVCGVSLDVGGKKEYLIAGKAEGDGKMHITLCDF IVPWDTL (residues 58–110 of SEQ ID NO:1) X2TTQKKSLNHRYQMGCECKITRCPMIPCYISSRDECLWMDWVTEK (residues 112–155 of SEQ ID NO:1) X3INGHQAKFFACIKRSDGSCAWYRGAAPPKQEFLDIEDP (residues 157–194 of SEQ ID NO:1)-Z 2 wherein X1 is the amino acid E or D, X2 is the amino acid T or I, X3 is the amino acid N or S, Z 1 is hydrogen or a substituent group or an arbitrary peptide having up to ten amino acids, and Z 2 is —OH, —NH 2 , substituted —NH 2 or an arbitrary peptide having up to ten amino acids, or b) the TIMP-2 of (a) modified by amidation, acylation, sulfation, phosphorylation, glycosylation, attachment of polyethylene-glycol groups, or a combination thereof, wherein the modified TIMP-2 has osteoblast stimulating activity after a bone fracture or surgical intervention, thereby stimulating osteoblasts.