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인제대학교 상계백병원

Proc. Natl. Acad. Sci. USA, Feb 20 2024, 121 (8) | https://doi.org/10.1073/pnas.2316871121 Heterogeneous osteoimmune profiles via single-cell transcriptomics in osteoporotic patients who fail bisphosphonate treatment

Byeong-Rak Keum^a,b,1, Hong Jin Kim^c,1, Juhun Lee^a, Minji Lee^d, Sin- Hyoung Hong^d,e, Ha Kyun Chang^f, Jin-Kwan Han^a, Sanguk Kim^a,g, Dong-Gune Chang^c,2, and Gun-Hwa Kim^b,d,e,h,2

^aDepartment of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea;

^bResearch Center for drug development, CYPHARMA Co., Ltd., Daejeon 34133, Korea;

^cDepartment of Orthopedic Surgery, Inje University Sanggye Paik Hospital, College of Medicine, Seoul 01757, Korea;

^dResearch Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, Korea;

^eDepartment of Bio-Analytical Science, University of Science and Technology, Daejeon 34113, Korea;

^fDepartment of Obstetrics and Gynecology, Korea University Ansan Hospital, College of Medicine, Seoul 15355, Korea;

^gInstitute of Convergence Science, Yonsei University, Seoul 03722, Korea; and

^hGraduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, Korea

¹B.-R.K. and H.J.K. contributed equally to this work.

²To whom correspondence may be addressed. : Dong-Gune Chang, Gun-Hwa Kim

Abstract

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.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-14)
연구진국내 연구진
분야 의약학 > 응용의학

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