Related Experiment Video

Updated: Jul 29, 2026

Osteoclast Derivation from Mouse Bone Marrow
06:17

Osteoclast Derivation from Mouse Bone Marrow

Published on: November 6, 2014

Abnormal osteoclast morphology and bone remodeling in a murine model of a lysosomal storage disease

M A Monroy1, F P Ross, S L Teitelbaum

  • 1Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Bone
|February 22, 2002
PubMed

Insights

Mucopolysaccharidosis type VII (MPS VII), a lysosomal storage disease, causes skeletal deformities due to impaired beta-glucuronidase activity. This study reveals abnormal osteoclast function and reduced bone formation in MPS VII mice, contributing to skeletal defects.

Area of Science:

  • Biochemistry
  • Genetics
  • Skeletal Biology

Background:

  • Mucopolysaccharidosis type VII (MPS VII) is a genetic lysosomal storage disorder resulting from beta-glucuronidase (GUSB) deficiency.
  • This deficiency leads to the accumulation of glycosaminoglycans, causing widespread tissue damage and skeletal deformities.
  • A murine model of MPS VII exhibits similar skeletal dysplasia to human patients.

Purpose of the Study:

  • To investigate the cellular and functional abnormalities of osteoclasts in MPS VII mice.
  • To determine the impact of GUSB deficiency on bone formation rates.
  • To elucidate the mechanisms underlying skeletal defects in MPS VII.

Main Methods:

  • Ultrastructural analysis of osteoclast morphology and bone surface interaction.
  • In vitro bone resorption assays using MPS VII and wild-type osteoclasts.
  • Bone marrow transplantation experiments to assess donor osteoclast function in MPS VII recipients.
  • In vivo calcein labeling to measure bone formation rates.

Main Results:

  • MPS VII osteoclasts exhibited abnormal morphology, including a lack of ruffled borders and detachment from bone.
  • Bone marrow transplantation normalized osteoclast morphology and function in MPS VII recipients.
  • MPS VII osteoclasts showed significantly reduced in vitro bone resorption capacity.
  • MPS VII mice displayed a slower rate of bone matrix deposition in the epiphysis.

Conclusions:

  • Abnormal osteoclast morphology and function, coupled with impaired bone matrix deposition, contribute to the skeletal dysplasia observed in MPS VII.
  • GUSB deficiency directly impacts osteoclast activity and bone formation, highlighting a critical role in skeletal integrity.
  • The MPS VII mouse model provides valuable insights into the pathogenesis of skeletal defects in this lysosomal storage disease.

More Related Videos

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

Related Concept Videos

Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...