Preclinical models for investigating how bone marrow adipocytes influence bone and hematopoietic cellularity

Abstract

Laboratory mice are a crucial preclinical model system for investigating bone marrow adipocyte (BMAd)-bone and BMAd-hematopoiesis interactions. In this review, we evaluate the suitability of mice to model common human diseases related to osteopenia or hematopoietic disorders, point out consistencies and discrepancies among different studies, and provide insights into model selection. Species, age, sex, skeletal site, and treatment protocol should all be considered when designing future studies.

Keywords: bone; bone marrow adipocyte; bone marrow adipose tissue; hematopoiesis; preclinical models.

Figure 1.. Postnatal development of bone marrow adipocytes (BMAds) in mice.

Mouse long bones (A) and 3^rd caudal vertebrae (B) were collected at 1, 4 and 8 weeks after birth. Bones were decalcified with 14% EDTA for 3 weeks and used for paraffin sectioning. Slides were stained with hematoxylin (nuclei) and eosin (cytoplasm). Photomicrographs were taken under 200x magnification.

Figure 2.. Suitability of preclinical models for BMAd-bone and BMAd-hematopoiesis studies.

Bone marrow adipocytes (BMAds) may serve as energy source or secrete adipokines/cytokines to influence bone resorption, bone formation, hematopoietic stem cell (HSC) maintenance and hematopoiesis. Many preclinical models have been used to investigate the relationship between BMAds and bone/hematopoiesis. However, each one has their own pros and cons. We reviewed the literature and ranked these models based on their consistencies with human studies and repeatability between different studies. + indicates less-recommended and ++++ indicates well-recommended.