Abstract: The present disclosure provides compositions and methods for treating vascular smooth muscle cell proliferation in a subject that does not have a deficiency of ectonucleotide pyrophosphatase phosphodiesterase-1 (ENPP1) resulting in a pathological disease of calcification or ossification by administering an ENPP1 agent or an ENPP3 agent.

Abstract: The key function of TNAP in bone is degradation of PPi to remove this mineralization inhibitor and provide free phosphate for apatite deposition. PC-1 is a direct antagonist of TNAP function. ANK also antagonizes TNAP-dependent matrix calcification. Specifically, the activity of PC-1 inhibits initial MV apatite deposition, but ANK inhibits propagation of apatite outside the MVs. Furthermore, loss of function of the two distinct skeletal TNAP antagonists, PC-1 and ANK, ameliorates TNAP deficiency-associated osteomalacia in vivo. Conversely, the hyperossification associated with both PC-1 null mice and ANK-deficient (ank/ank) mice is ameliorated by deficiency of TNAP in vivo.

Abstract: The present invention relates to improved diagnostic methods for early detection of a risk for developing an arthritic disorder in humans, and screening assays for therapeutic agents useful in the treatment of arthritic disorders, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, cellular responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.

Abstract: The present invention relates to improved diagnostic methods for early detection of a risk for developing an arthritic disorder in humans, and screening assays for therapeutic agents useful in the treatment of arthritic disorders, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, cellular responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.

Abstract: Methods of inhibiting calcification in meniscal and articular cartilage of the joints are disclosed. The methods include blocking the activation and activity of transglutaminases tTGase and Factor XIIIa. Furthermore, disclosed are methods for identifying agents that affect TGase activity and/or matrix calcification.

Abstract: The key function of TNAP in bone is degradation of PPi to remove this mineralization inhibitor and provide free phosphate for apatite deposition. PC-1 is a direct antagonist of TNAP function. ANK also antagonizes TNAP-dependent matrix calcification. Specifically, the activity of PC-1 inhibits initial MV apatite deposition, but ANK inhibits propagation of apatite outside the MVs. Furthermore, loss of function of the two distinct skeletal TNAP antagonists, PC-1 and ANK, ameliorates TNAP deficiency-associated osteomalacia in vivo. Conversely, the hyperossification associated with both PC-1 null mice and ANK-deficient (ank/ank) mice is ameliorated by deficiency of TNAP in vivo.

Abstract: The key function of TNAP in bone is degradation of PPi to remove this mineralization inhibitor and provide free phosphate for apatite deposition. PC-1 is a direct antagonist of TNAP function. ANK antagonizes TNAP-dependent matrix calcification. Specifically, the activity of PC-1 inhibits initial MV apatite deposition, but ANK inhibits propagation of apatite outside the MVs. Furthermore, loss of function of the two distinct skeletal TNAP antagonists, PC-1 and ANK, ameliorates TNAP deficiency-associated osteomalacia in vivo. Conversely, the hyperossification associated with both PC-1 null mice and ANK-deficient (ank/ank) mice is ameliorated by deficiency of TNAP in vivo.