# Single cell sequencing revealed parathyroid oxyphil cells are involved in osteoporosis under primary hyperparathyroidism

**Authors:** Xinguo Zhang, Ruifeng Bai, Minjuan Li, Zhigang Li, Xian Zhao, Renwei Cao, Shen Tan, Kaiyuan Cheng, Yejun Zha, Xieyuan Jiang, Shuai Lu

PMC · DOI: 10.3389/fendo.2025.1603955 · 2025-05-27

## TL;DR

Single cell sequencing found that parathyroid oxyphil cells are more active in osteoporosis patients with primary hyperparathyroidism.

## Contribution

This study identifies parathyroid oxyphil cells as key players in osteoporosis under primary hyperparathyroidism using single cell sequencing.

## Key findings

- Parathyroid oxyphil cells are more abundant in osteoporosis patients with primary hyperparathyroidism.
- Cell-cell interactions and pathways like IL2/STAT5 and WNT/β-catenin are upregulated in osteoporosis patients.
- 281 differentially expressed genes related to kinase activity were identified in osteoporosis patients.

## Abstract

To analyze the heterogeneity of parathyroid cells between patients with primary hyperparathyroidism (PHPT) osteoporosis and PHPT non-osteoporosis patients.

Resected parathyroid tissues were collected from PHPT patients of osteoporosis and non-osteoporosis. Single cell sequencing (SCS) to investigate cell types in parathyroid tissue involved in osteoporosis under PHPT. Further cell-cell interaction and communication, pseudotime trajectory analysis, sub-population analysis of parathyroid chief cells and parathyroid oxyphil cells, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional prediction analysis to confirm specific function of parathyroid cells.

Hallmark-IL2/STAT5 and WNT/β-catenin pathways were upregulated in parathyroid cells of osteoporosis patients. Highest interactions and cell-cell communications were enriched in parathyroid cells. Subcluster analysis disclosed overall highest 31.86% CXCL10-PCC parathyroid chief cells, but SPARCL1-OC parathyroid oxyphil cells were higher in osteoporosis patients. Pseudotime trajectory analysis displayed that parathyroid oxyphil cells were in abundance in osteoporosis patients. In total, 281 DEGs involved in kinase activity were identified in osteoporosis patients. Heatmap showed HSPA1A-OC parathyroid oxyphil cells are predominantly involved in numerous and strongest cell interactions. GO and KEGG enrichment revealed PTH, NOTCH, FGF, EGF and CD59 pathways were significantly up-regulated in all parathyroid subpopulations in osteoporosis patients.

Single cell sequencing revealed highest number of parathyroid cells in parathyroid tissue in patients suffering with PHPT osteoporosis. Parathyroid oxyphil cells are predominantly involved in osteoporosis under PHPT.

## Linked entities

- **Genes:** IL2 (interleukin 2) [NCBI Gene 3558], STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 6776], Wnt (protein Wnt-2) [NCBI Gene 100641115], ctnnb1.S (catenin beta 1 S homeolog) [NCBI Gene 380441], CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627], SPARCL1 (SPARC like 1) [NCBI Gene 8404], HSPA1A (heat shock protein family A (Hsp70) member 1A) [NCBI Gene 3303], PTH (parathyroid hormone) [NCBI Gene 5741], Notch (neurogenic locus notch homolog) [NCBI Gene 100616083], FGF (fibroblast growth factor) [NCBI Gene 582058], EGF (epidermal growth factor) [NCBI Gene 1950], CD59 (CD59 molecule (CD59 blood group)) [NCBI Gene 966]
- **Diseases:** osteoporosis (MONDO:0005298), primary hyperparathyroidism (MONDO:0010837)

## Full-text entities

- **Genes:** CD59 (CD59 molecule (CD59 blood group)) [NCBI Gene 966] {aka 16.3A5, 1F5, EJ16, EJ30, EL32, G344}, HSPA1A (heat shock protein family A (Hsp70) member 1A) [NCBI Gene 3303] {aka HEL-S-103, HSP70, HSP70-1, HSP70-1A, HSP70-2, HSP70.1}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, SPARCL1 (SPARC like 1) [NCBI Gene 8404] {aka MAST 9, MAST9, PIG33, SC1}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 6776] {aka MGF, STAT5}
- **Diseases:** osteoporosis (MESH:D010024), PHPT (MESH:D049950)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12148854/full.md

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Source: https://tomesphere.com/paper/PMC12148854