Wnt and BMP signaling pathways co ‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2

This study aims to test the involvement of Wnt, bone morphogenetic proteins (BMP) pathways, and empty spiracles homeobox 2 (EMX2) in osteoblast differentiation and MM development. Initially, differentially expressed genes in bone marrow mesenchymal stem cells (MSCs) from MM patients and healthy donors were identified using microarray ‐based gene expression profiling. The functional role of Wnt and BMP in MM was determined. Next, we focused on the co‐operative effects of Wnt and BMP on calcium deposition, alkaline phosphatase (ALP) activity, the number of mineralized nodules, and osteocalcin (OCN) content in MSCs. The express ion patterns of Wnt and BMP pathway–related genes, EMX2 and osteoblast differentiation‐related factors were determined to assess their effects on osteoblast differentiation. Furthermore, regulation of Wnt and BMP in ectopic osteogenesis was also investigated in vivo. An integrated genomic screen suggested that Wnt and BMP regularly co‐operate to regulate EMX2 and affect MM. EMX2 was downregulated in MSCs. The activated Wnt and BMP resulted in more calcium salt deposits, mineralized nodules, and a noted increased in ALP activity and OCN content by upregulating EMX2, leading to induced dif ferentiation of MSCs into osteoblasts. Collectively, this study demonstrated that Wnt and BMP pathways could co‐operatively stimulate differentiation of MSCs into osteoblasts and inhibit MM progression, representing potential targets for MM treatment.
Source: Journal of Cellular Biochemistry - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research