Dedifferentiation and degeneration of chondrocytes critically influences the efficiency of cartilage repair. One of the causes is the defect of transforming growth factor (TGF)-β signaling that promotes chondrogenic differentiation and degeneration. In the present study, we found that aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) negatively regulates TGF-β signaling via interactions with Smad2 and Smad3 in immunoprecipitation assay and luciferase assay. In addition, we observed that the AIMP1 expression level was significantly increased in osteoarthritis (OA) patient-derived degenerated chondrocytes compared with healthy control. So, we hypothesized that downregulation of AIMP1 using small-interfering RNA (siRNA) technology in dedifferentiated (collected at passage #6) and degenerated (obtained from OA-affected areas) chondrocytes could lead to recover TGF-β signaling in both chondrocytes. Indeed, AIMP1 downregulation restored TGF-β signaling by promoting phosphorylation of Smad2 and Smad3, which shows redifferentiated characteristics in both dedifferentiated and degenerated chondrocytes. Additionally, implantation analyses using in vivo mouse model clearly showed that AIMP1 downregulation resulted in the increased chondrogenic potential as well as the enhanced cartilage tissue formation in both dedifferentiated and degenerated chondrocytes. Histological analyses clarified that AIMP1 downregulation increased expression levels of collagen type II (Col II) and aggrecan, but not Col I expression. Taken together, these data indicate that AIMP1 downregulation using siRNA is a novel tool to restore TGF-β signaling and thereby increases the chondrogenic potential of dedifferentiated/degenerated chondrocytes, which could be further developed as a therapeutic siRNA to treat OA.

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Research SnippetsBCL2 and JUNB abnormalities in primary cutaneous lymphomas BCL2 is upregulated in nodal and extranodal B-cell nonHodgkin's lymphomas with a consequent anti-apoptotic effect. Mao et al. report a comprehensive study of BCL2 status in primary cutaneous lymphomas (PCL) and compare the results with that of JUNB, in which BCL2 loss and JUNB gain were present in a proportion of primary cutaneous T-cell lymphomas (CTCL), and BCL2 gain and JUNB loss in primary cutaneous B-cell lymphomas (PCBCL). These findings suggest that BCL2 and JUNB behave differently in CTCL and PCBCL and the future therapeutic strategy targeting BCL2 and JUNB should also be different for patients with CTCL and PCBCL. Mao X, Orchard G, Lillington DM et al. BCL2 and JUNB abnormalities in primary cutaneous lymphomas. Br J Dermatol 2004; 151: 546-556.

1161 11 Treister N, Lehmann LE, Cherrick I et al. Dyskeratosis congenital vs. chronic graft versus host disease: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98: 566 -571. 12 Baykal C, Kavak A, Gülkan P et al. Dyskeratosis congenita associated with three malignancies. J Eur Acad Dermatol Venereol 2003; 17: 216-218. 13 M'Kacher R, Laithier V, Valent A et al. Sensivity to radiation and alkylating agent of peripheral lymphocytes and fibroblasts in a Hoyeraal-Hreidarsson syndrome patient.

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