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Published on: March 22, 2024
Single-cell transcriptomics identifies CD36 as a negative regulator of osteogenic differentiation in murine
Weibin Wang1, Xinyou Han1, Qingsong Fu1
1Department of Orthopaedic Trauma, Ningbo No. 2 Hospital, Wenzhou Medical University, No. 41, Xibei Street, Haishu District, 315010 Ningbo, China.
Background:
Osteoporosis is characterized by impaired osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs). The molecular regulators driving this impairment in murine models remain incompletely understood.
Objectives:
To identify key regulators of BM-MSC osteogenic differentiation in murine osteoporosis using single-cell transcriptomic analysis, and to validate the functional role of the identified candidate in vivo.
Methods:
Single-cell RNA sequencing data from murine osteoporosis and osteoarthritis samples were analyzed to identify differentially expressed genes in BM-MSC subpopulations. CD36 was selected based on GO-KEGG enrichment analysis. Functional validation was performed in an ovariectomy mouse model using adeno-associated virus-mediated CD36 knockdown. Bone microarchitecture was assessed by micro-computed tomography and histomorphometry. Osteogenic capacity was evaluated by Western blot, immunofluorescence, and immunohistochemistry.
Results:
CD36 was significantly upregulated in BM-MSCs from murine osteoporotic samples. CD36-positive BM-MSCs showed enrichment of the peroxisome proliferator-activated receptor signaling pathway and extracellular matrix-receptor interaction pathways. Adeno-associated virus-mediated CD36 knockdown in ovariectomized mice restored trabecular bone parameters and increased RUNX2-positive osteoprogenitor numbers compared to controls.
Conclusions:
CD36 acts as a negative regulator of osteogenic differentiation in murine BM-MSCs. Targeting CD36 may represent a therapeutic strategy for osteoporosis by restoring the osteogenic/adipogenic balance in bone marrow.
Insights
CD36 negatively regulates bone formation by impairing osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs). Targeting CD36 may offer a new therapeutic approach for osteoporosis.
Area of Science:
- Stem cell biology
- Bone biology
- Molecular medicine
Background:
- Osteoporosis involves impaired osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs).
- Molecular mechanisms underlying this impairment in murine models are not fully understood.
Purpose of the Study:
- Identify key regulators of BM-MSC osteogenic differentiation in murine osteoporosis using single-cell transcriptomics.
- Validate the in vivo functional role of identified candidates.
Main Methods:
- Single-cell RNA sequencing of murine osteoporosis and osteoarthritis samples.
- Identification of differentially expressed genes and selection of CD36 via GO-KEGG analysis.
- In vivo validation using adeno-associated virus-mediated CD36 knockdown in an ovariectomy mouse model, assessing bone microarchitecture and osteogenic capacity.
Main Results:
- CD36 was significantly upregulated in BM-MSCs from osteoporotic murine samples.
- CD36-positive BM-MSCs showed enrichment in peroxisome proliferator-activated receptor signaling and extracellular matrix-receptor interaction pathways.
- CD36 knockdown in ovariectomized mice restored bone parameters and increased osteoprogenitor numbers.
Conclusions:
- CD36 acts as a negative regulator of osteogenic differentiation in murine BM-MSCs.
- Targeting CD36 could be a therapeutic strategy for osteoporosis by rebalancing osteogenic and adipogenic processes in bone marrow.
