Related Experiment Video
Updated: Aug 14, 2026
11:11
Isolation, Purification, and Differentiation of Osteoclast Precursors from Rat Bone Marrow
Published on: May 19, 2019
The epithelial Ca2+ channel TRPV5 is essential for proper osteoclastic bone resorption
Bram C J van der Eerden1, Joost G J Hoenderop, Teun J de Vries
1Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Summary
The epithelial calcium channel TRPV5 is essential for bone resorption. TRPV5 deficiency increases osteoclast size and number but impairs their ability to resorb bone, highlighting its role in transcellular calcium transport.
Area of Science:
- Bone Biology
- Cell Physiology
- Calcium Homeostasis
Background:
- Bone remodeling requires precise control of resorption and formation for bone mass maintenance.
- Transcellular calcium transport is crucial for both bone resorption and formation, but its molecular mechanisms are not fully understood.
- The epithelial calcium channel TRPV5, a highly calcium-selective transient receptor potential (TRP) channel, has an uncharacterized role in bone.
Purpose of the Study:
- To investigate the functional role of the epithelial calcium channel TRPV5 in bone remodeling, specifically in osteoclast function.
- To determine the localization and expression of TRPV5 in bone cells and its involvement in transcellular calcium transport during bone resorption.
Main Methods:
- Analysis of TRPV5 mRNA expression in human and murine bone samples and isolated osteoclasts.
- Immunostaining to confirm TRPV5 localization in murine osteoclasts.
- Phenotypic analysis of TRPV5 knockout (TRPV5(-/-)) mice, including bone section analysis and measurement of urinary bone resorption markers.
- In vitro studies using bone marrow cultures to assess osteoclast formation and a functional resorption pit assay to evaluate bone resorption activity.
Main Results:
- TRPV5 mRNA and protein were detected in osteoclasts, localized to the ruffled border membrane, but absent in osteoblasts.
- TRPV5(-/-) mice exhibited increased osteoclast numbers and area, alongside reduced urinary deoxypyridinoline levels, indicating altered bone resorption.
- In vitro, TRPV5 deficiency led to increased osteoclastogenesis but significantly impaired bone resorption activity.
- Functional assays confirmed that TRPV5 is essential for effective osteoclastic bone resorption.
Conclusions:
- TRPV5 is a critical epithelial calcium channel indispensable for functional osteoclastic bone resorption.
- TRPV5 deficiency results in compensatory increases in osteoclast size and number, but with severely compromised resorptive capacity.
- This study elucidates the significant role of transcellular calcium transport, mediated by TRPV5, in the regulation of osteoclast function and bone remodeling.
Related Concept Videos
01:31Osteoclasts 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...
01:17Hormones and Bone Tissue
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:21Skeleton and Calcium Homeostasis
Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
01:40Bone 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.
01:25Role of Vitamins in Maintaining Bone Health
The growth and maintenance of bone are regulated by a combination of nutritional factors, including vitamins, such as vitamin A, B12, C, D, and K.
Vitamin A
Vitamin A is involved in the process of bone remodeling. Retinoic acid, the active metabolite of Vitamin A, has nuclear receptors in osteoblasts and osteoclasts, which are involved in bone remodeling.
Vitamin B12
Vitamin B12 acts as a cofactor during the formation of osteoblast-related proteins, such as osteocalcin. Vitamin B12 plays a role...
Vitamin A
Vitamin A is involved in the process of bone remodeling. Retinoic acid, the active metabolite of Vitamin A, has nuclear receptors in osteoblasts and osteoclasts, which are involved in bone remodeling.
Vitamin B12
Vitamin B12 acts as a cofactor during the formation of osteoblast-related proteins, such as osteocalcin. Vitamin B12 plays a role...
01:27Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...