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Molecular profiling of bone remodeling occurring in musculoskeletal tumors
Author(s) -
Nakajima Kosei,
Kidani Teruki,
Miura Hiromasa
Publication year - 2021
Publication title -
journal of orthopaedic research®
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.24879
Subject(s) - bone morphogenetic protein 7 , cancer research , osteoclast , osteoblast , bone morphogenetic protein , bone morphogenetic protein 5 , osteocyte , bone morphogenetic protein 6 , osteosarcoma , bone morphogenetic protein 2 , alveolar soft part sarcoma , medicine , pathology , biology , sarcoma , receptor , genetics , gene , in vitro
Musculoskeletal malignancy is often accompanied by aberrant bone remodeling, leading to tumor cell invasion into skeletal tissues and causing severe pain. BMPs, FGF‐2, and RANKL have been identified as promising regulators in physiological bone remodeling. In this study, we explored the expressional profile of BMPs, FGF‐2, and RANKL in 1361 patients with 22 varieties of musculoskeletal tumors. Notably, the expression of FGF‐2 and RANKL was under detected in all patients. Among BMP1 to BMP15, we found that BMP1, BMP2, BMP4, BMP5, BMP6, and BMP7 were prevalent. In comparison with normal bones, osteosarcoma highly expressed BMP1, BMP2, BMP4, and BMP7 with statistical significance. Synovial sarcoma upregulated BMP4, BMP5, and BMP7; rhabdomyosarcoma increased BMP1 and BMP4; and alveolar soft part sarcoma upregulated BMP1, BMP4, and BMP7. To visualize the BMP‐oriented interactions in a bone tumor microenvironment, we have developed novel software that analyzes numerous cell‐to‐cell and ligand‐to‐receptor interactions, that is, Environmentome, delineating that osteosarcoma‐secreted BMP‐4 and synovial sarcoma‐secreted BMP7 potently interact with osteoblasts, osteocytes, osteoclast precursors, and mature osteoclasts. Specifically, quantification analysis revealed that the relationship between osteosarcoma and mature osteoclast/precursor, BMP4–BMPR2 and BMP4–ACVR2A interactions were most potent. Regarding the association between osteosarcoma and osteocyte/osteoblast, BMP4–ACVR1 and BMP4–BMPR2 were the key interactions. In the connection between synovial sarcoma and mature osteoclast/precursor, BMP7–ACVR2A and BMP7–BMPR2 interactions were most remarkable. With regard to the cellular link between synovial sarcoma and osteocyte/osteoblast, BMP7–BMPR2 was identified as a potent interaction. In conclusion, our new outlook suggests delivering the pathological events that clinically underlie behind severe skeletal pain or fracture in musculoskeletal tumors.