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Objective. Interleukin-10 (IL-10) is a pleiotropic immunoregulatory cytokine with a chondroprotective effect that is elevated in cartilage and synovium in patients with osteoarthritis. However, the role of IL-10 during endochondral bone formation and its mechanism of action have not been elucidated.Methods. IL-10 -/-mice and IL-10-treated tibial organ cultures were used to study loss and gain of IL-10 functions, respectively, during endochondral bone formation. Primary chondrocytes from the long bones of mouse embryos were cultured with and without IL-10. To assess the role of IL-10 in chondrogenic differentiation, we conducted mesenchymal cell micromass cultures.Results The main pathologic feature of osteoarthritis (OA) is gradual loss of cartilage from exposure to repetitive loading. The initial response of chondrocytes to external mechanical loading is adaptation; that is, they become metabolically active and proliferative (1). However, repetitive stress induces hypertrophic differentiation and, eventually, chondrocyte apoptosis. During this process, the balance between anabolic and catabolic signaling pathways in which SOX9 and RUNX-2, respectively, function as major regulatory transcription factors is critical in determining the fate of chondrocytes (2,3). Several cytokines can affect the expression of SOX9 and RUNX-2 via complex autocrine and paracrine loops and, as a consequence, have an effect on the progression of OA (4,5).The physiologic and pathologic roles of the main catabolic cytokines, such as interleukin-1␤ (IL-1␤) and tumor necrosis factor ␣ (TNF␣), have been well established in chondrocyte biology (4).

Dual immunoglobulin (Ig) domain-containing adhesion molecule (DICAM) is involved in cell-cell adhesion through a heterophilic interaction with aVb3 integrin, which suggests that DICAM may participate in osteoclast differentiation. DICAM was localized in the plasma membrane of RAW264.7 and THP-1 cells, and its expression gradually increased during osteoclastogenesis in mouse bone marrow-derived macrophages (BMMs) treated with receptor activator of nuclear factor k-B ligand (RANKL) and macrophage colonystimulating factor (M-CSF). Forced expression of DICAM in BMMs and RAW264.7 cells blocked the generation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts. Conversely, knockdown of DICAM by small hairpin RNA (shRNA) increased osteoclast formation in RAW264.7 cells. DICAM-mediated suppression of osteoclast differentiation was in part due to the inhibition of the p38 mitogenactivated protein (MAP) kinase pathway, which was corroborated by a decrease in the expression of c-Fos and nuclear factor of activated T cells (NFAT)c1. Mechanistically, DICAM directly interacted with integrin b3, which inhibited heterodimerization between integrin aV and b3. Exogenous expression of integrin b3 or high-dose M-CSF rescued DICAM-mediated inhibition of osteoclastogenesis, suggesting crosstalk between the integrin b3 and c-Fms pathways. Finally, recombinant DICAM ectodomain suppressed the RANKL-and M-CSFinduced osteoclastogenesis of BMMs. Collectively, these results indicate that DICAM acts as a negative regulator of osteoclast differentiation by suppressing the integrin aVb3 pathway. ß

ObjectiveThe technique of short segment pedicle screw fixation (SSPSF) has been widely used for stabilization in thoracolumbar burst fractures (TLBFs), but some studies reported high rate of kyphosis recurrence or hardware failure. This study was to evaluate the results of SSPSF including fractured level and to find the risk factors concerned with the kyphosis recurrence in TLBFs.MethodsThis study included 42 patients, including 25 males and 17 females, who underwent SSPSF for stabilization of TLBFs between January 2003 and December 2010. For radiologic assessments, Cobb angle (CA), vertebral wedge angle (VWA), vertebral body compression ratio (VBCR), and difference between VWA and Cobb angle (DbVC) were measured. The relationships between kyphosis recurrence and radiologic parameters or demographic features were investigated. Frankel classification and low back outcome score (LBOS) were used for assessment of clinical outcomes.ResultsThe mean follow-up period was 38.6 months. CA, VWA, and VBCR were improved after SSPSF, and these parameters were well maintained at the final follow-up with minimal degree of correction loss. Kyphosis recurrence showed a significant increase in patients with Denis burst type A, load-sharing classification (LSC) score >6 or DbVC >6 (p<0.05). There were no patients who worsened to clinical outcome, and there was no significant correlation between kyphosis recurrence and clinical outcome in this series.ConclusionSSPSF including the fractured vertebra is an effective surgical method for restoration and maintenance of vertebral column stability in TLBFs. However, kyphosis recurrence was significantly associated with Denis burst type A fracture, LSC score >6, or DbVC >6.

Collectively, DICAM suppressed angiogenesis by attenuating AKT and p38 MAP kinase signalling, which suggests that DICAM may be a novel negative regulator of angiogenesis.