# IGF-1 from bone marrow Adipoq-lineage cells stimulates endocortical bone formation in mature female mice

**Authors:** Joshua C Bertels, Jasmin Koehnken Sawall, Brian Dulmovits, Xiaobin Liu, Ashley Phan, Xing Ji, Fangfang Song, Christopher Thom, Fanxin Long

PMC · DOI: 10.1093/jbmrpl/ziag024 · 2026-02-14

## TL;DR

A specific type of bone marrow cell produces IGF-1, which helps build cortical bone in adult female mice.

## Contribution

Identifies Adipoq+ stromal cells as a local source of IGF-1 that specifically supports endocortical bone formation in mature females.

## Key findings

- IGF-1 from Adipoq+ cells in bone marrow promotes endocortical bone formation in mature female mice.
- Deleting IGF-1 in these cells reduces cortical bone mass without affecting trabecular bone or hematopoiesis.
- The effect is sex-specific and site-specific, with no impact on male mice or other bone parameters.

## Abstract

Insulin-like growth factor 1 (IGF-1) is an anabolic signal promoting growth, differentiation and function of both embryonic and postnatal tissues. Both endocrine and paracrine functions of IGF-1 have been documented to regulate bone growth and BM hematopoiesis. Local production of IGF-1 from various cell types may contribute differently to the overall bioactivity of IGF-1 in bone, but relevant sources and mechanisms are yet to be fully elucidated. Here, we report that the Adipoq+ stromal cells are a notable source of IGF-1 in the BM of postnatal mice. Deletion of IGF-1 with Adipoq-Cre diminished endocortical bone formation and cortical bone mass in mature female mice. On the other hand, the trabecular bone parameters or hematopoietic properties were not affected in mutant mice of either sex. The study uncovers a local source of IGF-1 in the BM microenvironment that contributes to bone anabolic regulation in a site-specific manner.

## Linked entities

- **Genes:** ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370], IGF1 (insulin like growth factor 1) [NCBI Gene 3479]
- **Proteins:** IGF1 (insulin like growth factor 1)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ly6g (lymphocyte antigen 6 family member G) [NCBI Gene 546644] {aka Gr-1, Gr1, Ly-6G}, Sp7 (Sp7 transcription factor 7) [NCBI Gene 170574] {aka 6430578P22Rik, C22, Osx}, Ly76 (lymphocyte antigen 76) [NCBI Gene 104231] {aka TER-119, Ter119}, Plin1 (perilipin 1) [NCBI Gene 103968] {aka 6030432J05Rik, Peri, Plin}, Mmp3 (matrix metallopeptidase 3) [NCBI Gene 17392] {aka EMS-2, MMP-3, SL-1, SLN-1, SLN1, STR-1}, Adipoq (adiponectin, C1Q and collagen domain containing) [NCBI Gene 11450] {aka 30kDa, APN, Acdc, Acrp30, Ad, Adid}, Tnfrsf11b (tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)) [NCBI Gene 18383] {aka OCIF, Opg, TR1}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Tcrb (T cell receptor beta chain) [NCBI Gene 21577] {aka TCRbeta, Tib}, Col1a2 (collagen, type I, alpha 2) [NCBI Gene 12843] {aka Col1a-2, Cola-2, Cola2, oim}, Nes (nestin) [NCBI Gene 18008] {aka ESTM46, Ifaprc2, Marc2, RC2}, Flt3 (FMS-like tyrosine kinase 3) [NCBI Gene 14255] {aka B230315G04, CD135, Flk-2, Flk2, Flt-3, Ly72}, Col2a1 (collagen, type II, alpha 1) [NCBI Gene 12824] {aka Col2, Col2a, Col2a-1, Del1, Dmm, Lpk}, Ly6a (lymphocyte antigen 6 family member A) [NCBI Gene 110454] {aka Ly-6A.2, Ly-6A/E, Ly-6E.1, Sca-1, Sca1, TAP}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, Ctrl (chymotrypsin-like) [NCBI Gene 109660] {aka 0910001G08Rik, 1810004D15Rik, Ctra-1, Ctra1, chymopasin, mFLJ00366}, Cd48 (CD48 antigen) [NCBI Gene 12506] {aka BCM1, BLAST, BLAST-1, BLAST1, Bcm-1, MEM-102}, Dmp1 (dentin matrix protein 1) [NCBI Gene 13406] {aka AG1, DMP-1, Dmp, PP}, Mpp4 (membrane protein, palmitoylated 4 (MAGUK p55 subfamily member 4)) [NCBI Gene 227157] {aka Dlg6}, Tnfsf11 (tumor necrosis factor (ligand) superfamily, member 11) [NCBI Gene 21943] {aka Ly109l, ODF, OPGL, RANKL, Trance}, Kit (Kit proto-oncogene receptor tyrosine kinase) [NCBI Gene 16590] {aka Bs, CD117, Fdc, Gsfsco1, Gsfsco5, Gsfsow3}, Cxcl12 (C-X-C motif chemokine ligand 12) [NCBI Gene 20315] {aka Pbsf, Scyb12, Sdf1, Tlsf, Tpar1}, Gh (growth hormone) [NCBI Gene 14599] {aka Gh1, Ghb1}, Sost (sclerostin) [NCBI Gene 74499] {aka 5430411E23Rik}, Nr1i3 (nuclear receptor subfamily 1, group I, member 3) [NCBI Gene 12355] {aka CAR, CAR-beta, Care2, ESTM32, MB67}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, Lepr (leptin receptor) [NCBI Gene 16847] {aka B219, LEP-R, LEPROT, Leprb, Modb1, OB-RGRP}, Hprt1 (hypoxanthine phosphoribosyltransferase 1) [NCBI Gene 15452] {aka HPGRT, Hprt}, Bglap2 (bone gamma-carboxyglutamate protein 2) [NCBI Gene 12097] {aka BGP2, Bglap1, Bgp, Og2, mOC-B}, Slamf1 (signaling lymphocytic activation molecule family member 1) [NCBI Gene 27218] {aka 4933415F16, CD150, CDw150, ESTM51, IPO-3, Slam}
- **Diseases:** growth retardation (MESH:D006130), intrauterine growth retardation (MESH:D005317), bone loss (MESH:D001847), adiposity (MESH:D018205), BMSC (MESH:D002292)
- **Chemicals:** TRIzol (MESH:C411644), Methylcellulose (MESH:D008747), F (MESH:D005461), Alexa Fluor 647 (MESH:C569686), CKMix50 (-), aluminum (MESH:D000535), calcein (MESH:C007740), chloroform (MESH:D002725), paraformaldehyde (MESH:C003043), sucrose (MESH:D013395), Alizarin Red S (MESH:C004468), ice (MESH:D007053), PBS (MESH:D007854)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** BMSC — Mus musculus (Mouse), Stromal cell line (CVCL_2128), C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965202/full.md

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Source: https://tomesphere.com/paper/PMC12965202