Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

Detection of DNA from a range of bacterial species in the knee joints of dogs with inflammatory knee arthritis and associated degenerative anterior cruciate ligament rupture.

Mixtures of bacterial nucleic acids can often be detected in synovial joints affected with arthritis. We investigated the potential role of such mixtures of bacterial nucleic acids in the pathogenesis of arthritis in a naturally occurring canine model. Dogs with a common inflammatory knee arthritis in which associated pathological degenerative anterior cruciate ligament (ACL) rupture often develops were studied. Synovial biopsies were obtained from 43 dogs with the naturally occurring ACL rupture arthropathy, 12 dogs with normal knees and intact ACL, and 16 dogs with normal knees and experimentally induced ACL rupture. Using PCR, specimens were tested for Borrelia burgdorferi OspA and p66 gene sequences. Broad-ranging 16S rRNA primers were also used; 'panbacterial' PCR products were cloned and multiple clones were sequenced for bacterial identification. Synovium was also studied histologically. The presence of bacterial DNA within the synovium was significantly associated with the naturally occurring ACL rupture arthropathy (p<0.05); knee joints from 37% of these dogs were PCR-positive. Mixtures of bacterial DNA were common and often included environmental bacteria; predominant organisms included Borrelia burgdorferi and Stenotrophomonas maltophilia. DNA from environmental bacteria was only found in dogs with the naturally occurring ACL rupture arthopathy; joints from 33% of affected dogs contained such bacterial DNA. Synovial inflammation developed in dogs with both naturally occurring and experimentally induced ACL rupture, when compared with intact ACL controls (p<0.01). These results indicate that mixtures of DNA derived from environmental bacteria are commonly found in the knee joint of a naturally occurring canine arthropathy, often in association with a recognized joint pathogen. Our results also suggest that knee instability alone is not responsible for this finding and have led us to hypothesize that mixtures of bacterial DNA are an important causative factor in the pathogenesis of inflammatory arthritis in this canine model.