Methods of using f-spondin as a biomarker for cartilage degenerative conditions and bone diseases

A method for screening, diagnosing or prognosing a bone condition, disease, disorder or degenerative condition in a subject, or for measuring bone degeneration or endochondral bone formation resulting from fracture, cancer, ageing, trauma or a sports related injury in a subject, wherein said condition, disorder or said degeneration is characterized by an alteration in the level of expression of F-spondin, said method comprising:

• (I) measuring an amount of an F-spondin gene or gene product, or a fragment thereof, in a tissue sample obtained from the subject, wherein said F-spondin gene or gene product is:
• (a) a DNA corresponding to any one of SEQ ID NOS:
• 1, 3 or 5 or a nucleic acid derived therefrom;
• (b) a protein comprising any one of SEQ ID NOS:
• 2, 4 or 6;
• (c) a nucleic acid comprising a sequence hybridizable to any one of SEQ ID NOS:
• 1,3 or 5, or their complements under conditions of high stringency, or a protein comprising a sequence encoded by said hybridizable sequence;
• (d) a nucleic acid at least 90% homologous to any one of SEQ ID NOS:
• 1, 3 or 5, or their complements as determined using the NBLAST algorithm;
• or a protein encoded thereby;
• and
• (II) comparing the amount of said F-spondin gene or gene product in said subject with the amount of F-spondin gene or gene product present in a normal tissue sample obtained from a subject who does not have a bone condition, disease, disorder or degenerative condition or in a predetermined standard, wherein an alteration in the amount of said F-spondin gene or gene product in said subject compared to the amount in the normal tissue sample or pre-determined standard indicates the presence of a bone condition, disease, disorder or degenerative condition in said subject.

A method of screening for an agent or a candidate compound that blocks or inhibits Fspondin expression or activity/function, the method comprising:

• (a) contacting the F-spondin molecule, or fragments thereof, or cells containing the F-spondin molecule, with an agent or a candidate compound, wherein said F-spondin molecule comprises the nucleic acid sequence of any one of SEQ ID NOS:
• 1, 3 or 5 and/or the amino acid sequence of any one of SEQ ID NOS:
• 2, 4 or 6;
• and
• (b) determining the level of F-spondin expression or activity/function in the presence or absence of the agent or candidate compound;
• wherein the agent or candidate compound is considered to be effective if the level of F-spondin expression or activity/function is lower in the presence of the agent or candidate compound as compared to in the absence of the agent or candidate compound.

A method of screening for an agent or a candidate compound capable of modulating the expression or activity/function of F-spondin, said method comprising:

• (a) contacting the F-spondin molecule, or a cell containing F-spondin, or a fragment thereof with said agent or candidate compound, wherein said F-spondin molecule is:
• (i) a DNA corresponding to any one of SEQ ID NOS:
• 1, 3 or 5;
• (ii) a protein comprising any one of SEQ ID NOS:
• 2, 4 or 6;
• (iii) a nucleic acid comprising a sequence hybridizable to any one of SEQ ID NOS:
• 1, 3 or 5, or a complement thereof under conditions of high stringency, or a protein comprising a sequence encoded by said hybridizable sequence;
• or
• (iv) a nucleic acid at least 90% homologous to any one of SEQ ID NOS:
• 1,3 or 5, or a complement thereof as determined using an NBLAST algorithm or a protein encoded thereby;
• (b) determining whether or not the agent or candidate compound modulates the expression or activity/function of the F-spondin molecule;
• wherein an agent or a candidate compound that increases the expression or activity/function of the F-spondin molecule, or a fragment thereof is considered to be an agonist of F-spondin, and wherein a candidate compound that decreases the expression or activity/function of the F-spondin molecule or a fragment thereof is considered to be an antagonist of F-spondin.