2. Academic Validation
  3. Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton

Bone marrow-derived IGF-1 orchestrates maintenance and regeneration of the adult skeleton

  • Proc Natl Acad Sci U S A. 2023 Jan 3;120(1):e2203779120. doi: 10.1073/pnas.2203779120.
Jianfang Wang 1,  Qiaoling Zhu 1,  Dandan Cao 1,  Qiqi Peng 1,  Xiaoying Zhang 1,  Chong Li 2 3,  Chen Zhang 3,  Bo O Zhou 4,  Rui Yue 1 5
Affiliations

Affiliations

  • 1 Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
  • 2 Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, Shanghai 200092, China.
  • 3 School of Medicine, Tongji University, Shanghai 200092, China.
  • 4 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
  • 5 Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200120, China.
PMID: 36577075 DOI: 10.1073/pnas.2203779120
Abstract

Insulin-like growth factor I (IGF-1) is a key regulator of tissue growth and development in response to growth hormone stimulation. In the skeletal system, IGF-1 derived from osteoblasts and chondrocytes are essential for normal bone development; however, whether bone marrow (BM)-resident cells provide distinct sources of IGF-1 in the adult skeleton remains elusive. Here, we show that BM stromal cells (BMSCs) and megakaryocytes/platelets (MKs/PLTs) express the highest levels of IGF-1 in adult long bones. Deletion of Igf1 from BMSCs by Lepr-Cre leads to decreased bone formation, impaired bone regeneration, and increased BM adipogenesis. Importantly, reduction of BMSC-derived IGF-1 contributes to fasting-induced marrow fat accumulation. In contrast, deletion of Igf1 from MKs/PLTs by Pf4-Cre leads to reduced bone formation and regeneration without affecting BM adipogenesis. To our surprise, MKs/PLTs are also an important source of systemic IGF-1. Platelet-rich plasma (PRP) from Pf4-Cre; Igf1f/fmice showed compromised osteogenic potential both in vivo and in vitro, suggesting that MK/PLT-derived IGF-1 underlies the therapeutic effects of PRP. Taken together, this study identifies BMSCs and MKs/PLTs as two important sources of IGF-1 that coordinate to maintain and regenerate the adult skeleton, highlighting reciprocal regulation between the hematopoietic and skeletal systems.

Keywords

IGF-1; adipogenesis; bone marrow; hematopoiesis; osteogenesis.

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