Differentially expressed proteins identified by TMT proteomics analysis in bone marrow microenvironment of osteoporotic patients.
We applied tandem mass tag (TMT)-based proteomics to investigate protein changes in bone marrow microenvironment of osteoporotic patients undergoing spine fusion. Multiple bioinformatics tools were used to identify and analyze 219 differentially expressed proteins. These proteins may be associated with the pathogenesis of osteoporosis.


INTRODUCTION
Bone marrow microenvironment is indispensable for the maintenance of bone homeostasis. We speculated that alterations of some factors in the microenvironment of osteoporotic subjects might influence the homeostasis. This study aimed to investigate the changes in the expression of protein factors in the bone marrow environment of osteoporosis.


METHODS
We performed a proteomics analysis in the vertebral body-derived bone marrow supernatant fluid from 8 Chinese patients undergoing posterior lumbar interbody fusion (4 osteoporotic vs. 4 non-osteoporotic) and used micro-CT to analyze the microstructural features of spinous processes from these patients. We further performed western blotting to validate the differential expressions of some proteins.


RESULTS
There was deteriorated bone microstructure in osteoporotic patients. Based on proteomics analysis, 172 upregulated and 47 downregulated proteins were identified. These proteins had multiple biological functions associated with osteoblast differentiation, lipid metabolism, and cell migration, and formed a complex protein-protein interaction network. We identified five major regulatory mechanisms, splicing, translation, protein degradation, cytoskeletal organization, and lipid metabolism, involved in the pathogenesis of osteoporosis.


CONCLUSIONS
There are various protein factors, such as DDX5, PSMC2, CSNK1A1, PLIN1, ILK, and TPM4, differentially expressed in the bone marrow microenvironment of osteoporotic patients, providing new ideas for finding therapeutic targets for osteoporosis.
['Zhou|Q|Q|', 'Xie|F|F|', 'Zhou|B|B|', 'Wang|J|J|', 'Wu|B|B|', 'Li|L|L|', 'Kang|Y|Y|', 'Dai|R|R|http://orcid.org/0000-0001-7806-1602', 'Jiang|Y|Y|']
D015519:Bone Density D001853:Bone Marrow D005260:Female D005786:Gene Expression Regulation D006801:Humans D008159:Lumbar Vertebrae D008297:Male D008875:Middle Aged D010024:Osteoporosis D011506:Proteins D040901:Proteomics D013048:Specimen Handling D016103:Spinal Fractures D013123:Spinal Fusion D053719:Tandem Mass Spectrometry D055114:X-Ray Microtomography
Proteomics Bone marrow microenvironment Osteoporosis Bone marrow supernatant fluid Bone microstructure