Abstract: The invention provides methods and compositions for inhibiting, reducing or slowing inflammation or inflammatory arthritis, for treating inflammatory arthritis such as rheumatoid arthritis, psoriatic arthritis, and a spondyloarthropathy, for inhibiting, reducing or slowing osteoclast differentiation, function, or biological activity, for inhibiting or reducing persistence or accumulation of macrophages at an inflamed site or in an inflamed tissue or for promoting or increasing the efflux of macrophages from an inflamed site or an inflamed tissue, for increasing, stimulating, or promoting lymphocyte cell adhesion, for increasing, stimulating, or promoting lymphocyte efflux from a site of inflammation or from an inflamed tissue, and for decreasing, inhibiting, or reducing a lymphocyte cellular response by inhibiting, inhibiting the biological activity of or antagonizing an axonal guidance protein or a receptor thereof. The axonal guidance protein may be a netrin such as netrin-1, and its receptor may be unc5b.

Abstract: The invention provides methods and compositions for stimulating or promoting bone generation and regeneration, for stimulating or increasing differentiation, activation or function of osteoblasts, for inhibiting or decreasing differentiation, activation or function of osteoclasts, and for treating bone diseases such as osteonecrosis by administering to a subject a therapeutically effective amount of a pro-nerve growth factor (proNGF) or a pro-brain derived neurotrophic factor (proBDNF) or an analog, homolog, fragment or derivative thereof. The pro-nerve growth factor (proNGF) or a pro-brain derived neurotrophic factor (proBDNF) or an analog, homolog, fragment or derivative thereof may be a mutated or poorly hydrolyzed form of proNGF or proBDNF.

Abstract: The invention provides methods and compositions for reducing or inhibiting osteolysis, bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that inhibits the biological activity of an axon guidance protein. The compound or agent my inhibit transcription or translation of or bind to an axon guidance protein, such as, for instance, a netrin like netrin-1. Likewise, the compound or agent may inhibit transcription or translation of or bind to a receptor of an axon guidance protein, such as, for instance, a netrin receptor such as unc5b. In some instances, the compound or agent is an agonist of an adenosine A2A receptor. The invention also extends to pharmaceutical compositions comprising such compounds and agents.

Abstract: The invention provides methods and compositions for stimulating or promoting bone regeneration or repairing bone fracture or for stimulating or increasing differentiation or activation of osteoblasts by administering to a subject a therapeutically effective amount of an adenosine receptor agonist, or an analog, derivative or combination thereof, an adenosine receptor antagonist, or an analog, derivative or combination thereof, or adenosine or a compound that upregulates, increases the amount of or increases the biological activity of adenosine. The invention also extends to pharmaceutical compositions such as those comprising an agent that modulates an adenosine receptor such as an adenosine A2A agonist or A1 antagonist.

Abstract: The invention provides methods and compositions for reducing or inhibiting osteolysis, bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that inhibits the biological activity of an axon guidance protein. The compound or agent my inhibit transcription or translation of or bind to an axon guidance protein, such as, for instance, a netrin like netrin-1. Likewise, the compound or agent may inhibit transcription or translation of or bind to a receptor of an axon guidance protein, such as, for instance, a netrin receptor such as unc5b. In some instances, the compound or agent is an agonist of an adenosine A2A receptor. The invention also extends to pharmaceutical compositions comprising such compounds and agents.

Abstract: The invention provides methods and compositions for reducing or inhibiting bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that modulates an adenosine receptor such as the adenosine A2A receptor, in particular, an agonist of an adenosine A2A receptor. The invention also extends to pharmaceutical compositions comprising such an agent that modulates an adenosine receptor such as an adenosine A2A agonist and to prosthetic devices containing such an agent that modulates an adenosine receptor such as an A2A agonist on one or more surfaces or within the prosthetic device such as, for example, suspended in the cement forming the prosthetic device.

Abstract: The invention provides methods and compositions for reducing or inhibiting bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that modulates an adenosine receptor such as the adenosine A2A receptor, in particular, an agonist of an adenosine A2A receptor. The invention also extends to pharmaceutical compositions comprising such an agent that modulates an adenosine receptor such as an adenosine A2A agonist and to prosthetic devices containing such an agent that modulates an adenosine receptor such as an A2A agonist on one or more surfaces or within the prosthetic device such as, for example, suspended in the cement forming the prosthetic device.