No abstract

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common form of human myelopathy caused by a compression of the spinal cord by ectopic ossification of spinal ligaments. To elucidate the genetic basis for OPLL, we have been studying the ttw (tiptoe walking; previously designated twy) mouse, a naturally occurring mutant which exhibits ossification of the spinal ligaments very similar to human OPLL (refs 3,4). Using a positional candidate-gene approach, we determined the ttw phenotype is caused by a nonsense mutation (glycine 568 to stop) in the Npps gene which encodes nucleotide pyrophosphatase. This enzyme regulates soft-tissue calcification and bone mineralization by producing inorganic pyrophosphate, a major inhibitor of calcification. The accelerated bone formation characteristic of ttw mice is likely to result from dysfunction of NPPS caused by predicted truncation of the gene product, resulting in the loss of more than one-third of the native protein. Our results may lead to novel insights into the mechanism of ectopic ossification and the aetiology of human OPLL.

The present results demonstrate that a sufficient posterior shift of the spinal cord and neurologic improvement will not be obtained after posterior decompression surgery in the K-line (-) group. Our new index, the K-line, is a simple and practical tool for making decisions regarding the surgical approach for cervical OPLL patients.

The spontaneous dominant mouse mutant, Elbow-knee-synostosis (Eks), exhibits elbow and knee joint synosotsis, and premature fusion of cranial sutures. Here we identify a missense mutation in the Fgf9 gene that is responsible for the Eks mutation. Through investigation of the pathogenic mechanisms of joint and suture synostosis in Eks mice, we identify a key molecular mechanism that regulates FGF9 signaling in developing tissues. We show that the Eks mutation prevents homodimerization of the FGF9 protein and that monomeric FGF9 binds to heparin with a lower affinity than dimeric FGF9. These biochemical defects result in increased diffusion of the mutant FGF9 protein (FGF9Eks) through developing tissues, leading to ectopic FGF9 signaling and repression of joint and suture development. We propose a mechanism in which the range of FGF9 signaling in developing tissues is limited by its ability to homodimerize and its affinity for extracellular matrix heparan sulfate proteoglycans.

These results demonstrated that the surgical outcome of ASF was superior to the surgical outcome of laminoplasty. Elderly patients treated with laminoplasty showed an especially poor surgical outcome. We suggest that hypermobility of vertebrae at the cord compression level is a risk factor for poor surgical outcome after laminoplasty. Based on these results, we recommend that ASF should be the first choice of treatment for patients with significant ossification of the posterior longitudinal ligament and a hypermobile cervical spine. When laminoplasty is used for such cases, the addition of posterior instrumented fusion would be desirable for stabilizing the spine and decreasing damage to the spinal cord.