# Control of bone physiology by a novel type of adipose cells

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $470,143

## Abstract

Project Summary
 Osteoporosis and low bone mass are common chronic disorders associated with significant morbidity and
substantial healthcare costs. Bone is a dynamic tissue that constantly undergoes coupled remodeling by
osteoblasts and osteoclasts. Bone marrow (BM) adipocytes, arising from the same mesenchymal stem cells
(MSCs) as osteoblasts, also play a crucial role in bone homeostasis. Therefore, advancing our knowledge on
mesenchymal populations in bone and understanding their functions will reveal novel targets that address the
unmet clinical need for improved treatments for skeletal diseases. By carrying out large scale single cell
transcriptome analysis, we recently computationally defined the hierarchy of BM mesenchymal lineage cells
and delineated the in vivo differentiation process of MSCs through multiple intermediate subpopulations.
Interestingly, we identified a new subpopulation situated after proliferative mesenchymal progenitors and
before classic lipid-laden adipocytes (LiLAs) along the adipogenic differentiation route, and thus named those
cells marrow adipogenic lineage precursors (MALPs). These non-proliferative cells express mature adipocyte
markers, including Adiponectin (Adipoq), but do not accumulate lipid. In young mice, MALPs, genetically
labelled by Adipoq-Cre(ER), exist abundantly as BM stromal cells and capillary pericytes. Morphologically, they
display many long cell processes that make contacts among themselves and with surrounding cells, as well as
the bone surface, to establish a ubiquitous 3D network inside BM cavity. Cell ablation revealed that these
Adipoq+ cells play critical roles in maintaining BM vasculature and in suppressing bone formation. Strikingly,
MALPs are rapidly and transiently expanded after focal radiation, implying a reparative role during injury
response. One important feature of MALPs is that they highly express many secreted factors, such as VEGFa,
RANKL (Tnfsf11), CSF1, Cxcl12 etc, indicating regulatory actions on surrounding cells. These data lead to our
central hypothesis that MALPs represent a novel adipose cell type with pivotal roles in regulating their BM
environment during skeletal development, homeostasis, aging, and injury repair. Bone marrow adipose tissue
(MAT) normally refers to LiLAs, and current MAT research centers on their energy and lipid-related roles. This
proposal will expand the concept of MAT to include MALPs, a much more abundant cell population, and its
non-lipid-associated actions. Our aims are to: 1) determine the in vivo fate and properties of MALPs; 2)
elucidate the role of MALPs in regulating bone marrow vasculature; 3) determine the regulatory actions of
MALPs on bone resorption. Innovative approaches, such as single nucleus RNA-sequencing (snRNA-seq),
confocal 3D imaging, RNA FISH, genetically modified and reporter animal models, will be used throughout the
proposal. Our project will comprehensively characterize a novel mesenchymal subpopulation and its
mult...

## Key facts

- **NIH application ID:** 10233046
- **Project number:** 1R01AG069401-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ling Qin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $470,143
- **Award type:** 1
- **Project period:** 2021-05-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233046

## Citation

> US National Institutes of Health, RePORTER application 10233046, Control of bone physiology by a novel type of adipose cells (1R01AG069401-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10233046. Licensed CC0.

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