Molecular profiling of bone remodeling occurring in musculoskeletal tumors.
Bone Morphogenetic Proteins
/ metabolism
Bone Neoplasms
/ metabolism
Bone Remodeling
Bone and Bones
/ metabolism
Chondrosarcoma
/ metabolism
Fibroblast Growth Factors
/ metabolism
Humans
Multiple Myeloma
/ metabolism
Muscle Neoplasms
/ metabolism
Osteosarcoma
/ metabolism
RANK Ligand
/ metabolism
Tumor Microenvironment
BMPs
bone remodeling
musculoskeletal tumors
visualization of bone microenvironment
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
30
09
2020
received:
17
07
2020
accepted:
06
10
2020
pubmed:
10
10
2020
medline:
8
9
2021
entrez:
9
10
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Bone Morphogenetic Proteins
0
FGF20 protein, human
0
RANK Ligand
0
TNFSF11 protein, human
0
Fibroblast Growth Factors
62031-54-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1402-1410Informations de copyright
© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.
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