ArticleeLife2022
SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 41 citations in OpenAlex.
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- Wen-Shen-Tong-Luo-Zhi-Tong Decoction alleviates bone loss in aged mice by suppressing LONP1-mediated macrophage senescence.Pharmaceutical biology · 2025Article
- Impact of reactive oxygen species on bone regeneration in diabetes: Mechanisms and therapeutic strategies.Redox biology · 2025Review
- Accelerated osteocytic citrate production in chronic kidney disease is associated with protection of the kidney.bioRxiv : the preprint server for biology · 2025Article
- Metabotissugenic citrate biomaterials orchestrate bone regeneration via citrate-mediated signaling pathways.Science advances · 2025Article
- Current cutting-edge omics techniques on musculoskeletal tissues and diseases.Bone research · 2025Review
- The facilitated osteogenic differentiation by extracellular proline treatment in in vitro cell cultivation using MC3T3E1 and hPDLF.Genes & genomics · 2025Article
- Integrating 16S rRNA Gene Sequencing and Metabolomics Analysis to Reveal the Mechanism of L-Proline in Preventing Autism-like Behavior in Mice.Nutrients · 2025Article
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- Metabolic control of collagen synthesis.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- Interfaces between Cranial Bone and AISI 304 Steel after Long-Term Implantation: A Case Study of Cranial Screws.ACS biomaterials science & engineering · 2024Article
- Metabolic regulation of skeletal cell fate and function.Nature reviews. Endocrinology · 2024Review
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- Short- and long-term exposure to high glucose induces unique transcriptional changes in osteoblasts in vitro.Biology open · 2024Article
- Phenotypic plasticity - Implications for tumours in bone.Journal of bone oncology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Cellular differentiation is associated with the acquisition of a unique protein signature that is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that arise during differentiation. Using a bioinformatic approach, we discovered that osteoblast differentiation is associated with increased demand for the amino acid proline. When compared to other differentiated cells, osteoblast-associated proteins, including RUNX2, OSX, OCN, and COL1A1, are significantly enriched in proline. Using a genetic and metabolomic approach, we demonstrate that the neutral amino acid transporter SLC38A2 acts cell-autonomously to provide proline to facilitate the efficient synthesis of proline-rich osteoblast proteins. Genetic ablation of SLC38A2 in osteoblasts limits both osteoblast differentiation and bone formation in mice. Mechanistically, proline is primarily incorporated into nascent protein with little metabolism observed. Collectively, these data highlight a requirement for proline in fulfilling the unique biosynthetic requirements that arise during osteoblast differentiation and bone formation.
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Registered trials
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