Bone has an enormous capacity for growth, regeneration, and remodeling. This capacity is largely due to induction of osteoblasts that are recruited to the site of bone formation. The recruitment of osteoblasts has not been fully elucidated, though the immediate environment of the cells is likely to play a role via cell– matrix interactions. We show here that heparin-binding growth-associated molecule (HB-GAM), an extracellular matrix–associated protein that enhances migratory responses in neurons, is prominently expressed in the cell matrices that act as target substrates for bone formation. Intriguingly, N-syndecan, which acts as a receptor for HB-GAM, is expressed by osteoblasts/osteoblast precursors, whose ultrastructural phenotypes suggest active cell motility. The hypothesis that HB-GAM/N-syndecan interaction mediates osteoblast recruitment, as inferred from developmental studies, was tested using osteoblast-type cells that express N-syndecan abundantly. These cells migrate rapidly to HB-GAM in a haptotactic transfilter assay and in a migration assay where HB-GAM patterns were created on culture wells. The mechanism of migration is similar to that previously described for the HB-GAM–induced migratory response of neurons. Our hypothesis that HB-GAM/N-syndecan interaction participates in regulation of osteoblast recruitment was tested using two different in vivo models: an adjuvant-induced arthritic model and a transgenic model. In the adjuvant-induced injury model, the expression of HB-GAM and of N-syndecan is strongly upregulated in the periosteum accompanying the regenerative response of bone. In the transgenic model, the HB-GAM expression is maintained in mesenchymal tissues with the highest expression in the periosteum. The HB-GAM transgenic mice develop a phenotype characterized by an increased bone thickness. HB-GAM may thus play an important role in bone formation, probably by mediating recruitment and attachment of osteoblasts/osteoblast precursors to the appropriate substrates for deposition of new bone.

Acetabular dysplasia (AD) is a well-known cause of osteoarthritis (OA) of the hip, with its prevalence previously determined on plain radiography. The prevalence of preexisting AD was reported as 7.3% in a patient-based Asian population. Although computed tomography (CT) could evaluate AD in multiple planes, its prevalence using multiplanar CT images has not been reported. We investigated its prevalence with CT on coronal, axial, and sagittal planes and then determined if adding the axial and sagittal planes enhanced the investigation. We retrospectively examined 52 consecutive Japanese individuals (mean age 59.4 years) who had undergone CT for conditions unrelated to hip disorders. The inclusion criteria of CT images were (1) reconstructed axial slice thickness of ≤1 mm and (2) normal pelvic rotations and tilt. Exclusion criteria were (1) age <20 years, (2) neither hip center could be clearly detected, (3) evidence of hip OA. The parameters used to define AD on the coronal plane were the center–edge angle, Sharp angle, acetabular index, acetabular depth ratio, and acetabulum head index. The anterior and posterior acetabular sector angles were used as axial parameters and the vertical-center-anterior margin angle as the sagittal parameter. AD prevalence was calculated using multiplanar images and then compared with the previously reported Asian prevalence using 95% confidence intervals (CI). In this study, we defined “prevalence” as the proportion of subjects who had AD in at least one hip. The mean prevalence of AD on coronal, axial, and sagittal planes was 16.9, 15.4, and 7.7%, respectively. The lowest prevalence found by combining the three planes was 25.0% (95% CI 15.2–38.2%). This prevalence was significantly higher than that in the previously reported Asian population (7.3%). At the lowest estimate, the prevalence of AD evaluated in three planes was more than twice as high as the previously reported prevalence in Asians when we investigated its prevalence using multiplanar images. The prevalence of AD in the axial and sagittal planes was not negligible. We therefore suggest that it is important to add axial and sagittal planes’ data when investigating the prevalence of AD.

Triggering of the flexor tendon at the wrist is rare. We report a case of intrasynovial lipoma that caused a trigger wrist. As far as we know it is unique in that the intrasynovial lipoma simultaneously caused carpal tunnel syndrome. The massive tenosynovitis and adhesion of flexors tendons after the locking of the intrasynovial lipoma may have resulted from inflammation caused by attrition within the carpal tunnel.

Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl⁻ current (I_Cl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of I_Cl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl⁻ conductance. The TNFα-evoked Cl⁻ current exhibited electrophysiological and pharmacological properties similar to those of I_Cl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited I_Cl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA.