Disease relevance of Wisp1

• We previously isolated a partial cDNA fragment of a novel gene, Elm1 (expressed in low-metastatic cells), that is expressed in low-metastatic but not in high-metastatic K-1735 mouse melanoma cells [1].
• 3. WISP-1 genomic DNA was amplified in colon cancer cell lines and in human colon tumors and its RNA overexpressed (2- to >30-fold) in 84% of the tumors examined compared with patient-matched normal mucosa [2].

High impact information on Wisp1

• Elm1 was highly conserved, expressed ubiquitously in diverse organs, and mapped to mouse chromosome 15 [1].
• The WISP-1 gene was localized to human chromosome 8q24.1-8q24 [2].
• Using in situ and cell binding analysis, we demonstrated WISP-1 interaction with perichondral mesenchyme and undifferentiated chondrocytes [3].
• In vitro, we showed that WISP-1 expression in differentiating osteoblasts promotes BMP-2-induced osteoblastic differentiation [3].
• Therefore, we propose that WISP-1 plays an important regulatory role during bone development and fracture repair [3].

Biological context of Wisp1

• During embryonic development, WISP-1 expression was restricted to osteoblasts and to osteoblastic progenitor cells of the perichondral mesenchyme [3].
• Our data demonstrate that WISP-1 is an osteogenic potentiating factor promoting mesenchymal cell proliferation and osteoblastic differentiation while repressing chondrocytic differentiation [3].
• WISP-1 binding was restricted to the stroma of colon tumors and to cells with a fibroblastic phenotype [4].
• Fibroblasts expressed the growth-related genes lymphocyte antigen 6 complex locus-A and preprokephalin-1, and myofibroblasts expressed annexin-A8, WNT1-inducible signaling pathway protein-1, arginosuccinate synthetase-1, and procollagen XI of late-stage wound healing [5].

Anatomical context of Wisp1

• We evaluated the effect of WISP-1 on chondrocytes by generating stably transfected mouse chondrocytic cell lines [3].
• By using a solid phase assay, we showed that human skin fibroblast conditioned media contained WISP-1 binding factors [4].

Associations of Wisp1 with chemical compounds

• Similarly, WISP-1 interaction with human skin fibroblasts was inhibited by dermatan sulfate, decorin, and biglycan or by treatment of the cell surface with dermatan sulfate-specific lyases [4].

Other interactions of Wisp1

• This result was subsequently confirmed by real-time quantitative RT-PCR (IGF-1; 0.74+/-0.08 and 0.56+/-0.08, WISP-1; 0.71+/-0.03 and 0.56+/-0.08, and VEGF-C; 0.67+/-0.01 and 0.80+/-0.07, mean+/-SEM, compared with the control at zero and two days after induction of differentiation, respectively) [6].

References