Heterogeneous osteoimmune profiles via single- cell transcriptomics in osteoporotic patients who fail bisphosphonate treatment

• 成果类型: Article
• 署名作者: Keum, Byeong - Rak; Kim, Hong Jin; Lee, Juhun; Lee, Minji; Hong, Sin - Hyoung; Chang, Ha Kyun; Han, Jin - Kwan; Kim, Sanguk; Chang, Dong - Gune; Kim, Gun - Hwa
• 署名单位: Pohang University of Science & Technology (POSTECH); Inje University; Korea Basic Science Institute (KBSI); University of Science & Technology (UST); Korea University; Korea University Medicine (KU Medicine); Yonsei University; Chungnam National University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11900
• DOI: 10.1073/pnas.2316871121
• 发表日期: 2024-02-20
• 关键词: roles

摘要

Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single - cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non- osteoporotic, osteoporosis improved after BP treatment, and BP- failed cases. We found an increase in myeloid cells in patients with osteoporosis (specifically, T cell receptor+ macrophages). Furthermore, lymphoid lineage cells varied significantly, notably elevated natural killer cells (NKs) in the BP- failed group. Moreover, we provide fruitful lists of biomarkers within the immune cells that exhibit condition- dependent differences. The existence of osteoporotic- and BP- failure- specific cellular information flows was revealed by cell-cell interaction analysis. These findings deepen our insight of the osteoporosis pathology enhancing comprehension of the role of immune heterogeneity in postmenopausal osteoporosis and BP treatment failure.