Related Experiment Video
Updated: Aug 11, 2026
07:03
A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro
Published on: June 16, 2022
Calpain is required for normal osteoclast function and is down-regulated by calcitonin
Marilena Marzia1, Riccardo Chiusaroli, Lynn Neff
1Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut 06520-8044, USA.
The Journal of Biological Chemistry
|February 8, 2006
Summary
Calpain activity is essential for osteoclast function, including motility and bone resorption. Calcitonin inhibits osteoclast activity by down-regulating calpain, impacting bone remodeling.
Area of Science:
- Cell Biology
- Biochemistry
- Bone Biology
Background:
- Osteoclast motility relies on dynamic podosome structures.
- Calpains are implicated in focal adhesion dynamics and cytoskeletal regulation.
Purpose of the Study:
- To investigate the role of calpains (mu-calpain and m-calpain) in osteoclast motility and bone resorption.
- To elucidate the mechanism by which calcitonin affects osteoclast activity.
Main Methods:
- Utilized calpain inhibitors and mu-calpain knockout cells.
- Analyzed podosome belt integrity, substrate cleavage (filamin A, talin, Pyk2), osteoclast motility, and bone resorption.
- Performed histomorphometric analysis of mouse tibias and in vitro cell survival assays.
- Investigated the effect of calcitonin on osteoclast parameters and calpain activity.
Main Results:
- Calpain inhibitors and mu-calpain deficiency reduced osteoclast motility and bone resorption.
- Calpain inhibition disrupted podosome belts and induced osteoclast retraction.
- Mu-calpain knockout mice exhibited increased osteoclast numbers and decreased bone volume.
- Calcitonin mimicked calpain inhibitor effects and reduced osteoclast activity by inhibiting calpain.
Conclusions:
- Calpain activity is crucial for osteoclast motility, podosome dynamics, and bone resorption.
- Calcitonin exerts its bone-resorbing inhibitory effects, in part, by down-regulating calpain activity in osteoclasts.
Related Concept Videos
00:51Synthesis and Functions of Calcitonin
Calcitonin, a vital polypeptide hormone, regulates calcium levels within body fluids. It is released by the parafollicular cells, also known as C cells, situated in the follicular epithelium of the thyroid gland. Calcitonin responds to fluctuations in blood calcium levels and the influence of gastrointestinal hormones like gastrin and cholecystokinin.
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
The exact mechanisms by which calcitonin operates in calcium homeostasis remain elusive, but its significance is evident in several vital...
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...
01:31Osteoclasts 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...
01:21Skeleton 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.
00:59The Parathyroid Glands
The two pairs of parathyroid glands embedded within the posterior surface of the thyroid gland are restricted by a dense capsule around them. These glands comprise two distinct cell populations—parathyroid oxyphil and parathyroid principal cells- pivotal in calcium homeostasis.
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by producing...
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by producing...
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.