Related Experiment Video
Updated: Jun 5, 2026
11:47
A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
Published on: June 8, 2014
Plasminogen/plasmin modulates bone metabolism by regulating the osteoblast and osteoclast function
Yosuke Kanno1, Akira Ishisaki, Eri Kawashita
1Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science, Doshisha Women's Collage of Liberal Arts, 97-1 Kodo Kyo-tanabe, Kyoto 610-0395, Japan. ykanno@dwc.doshisha.ac.jp
The Journal of Biological Chemistry
|January 18, 2011
Summary
Plasminogen absence increases osteoclast precursors and bone loss by suppressing osteoprotegerin. Restoring plasmin levels normalizes bone metabolism, suggesting new therapies for fibrinolytic bone diseases.
Area of Science:
- Biochemistry
- Bone Biology
- Fibrinolysis
Background:
- Plasminogen (Plg) and plasmin are implicated as key regulators of bone metabolism.
- Their precise role in osteoblast (OB) and osteoclast (OC) function requires further elucidation.
Purpose of the Study:
- To investigate the impact of plasminogen absence on osteoblast and osteoclast function.
- To explore the therapeutic potential of plasmin in modulating bone metabolism.
Main Methods:
- Comparative analysis of bone marrow-derived cells from Plg(-/-) and wild-type (WT) mice.
- Assessment of osteoclastogenesis in co-culture systems involving OBs and RAW264.7 cells.
- Evaluation of osteoprotegerin expression in OBs with and without exogenous plasmin treatment.
Main Results:
- Plg(-/-) mice exhibited a larger pre-osteoclast population and suppressed osteoprotegerin expression in osteoblasts.
- Exogenous plasmin induced osteoprotegerin expression in Plg(-/-) osteoblasts.
- Osteoclastogenesis was accelerated in co-cultures with Plg(-/-) osteoblasts, an effect reversed by exogenous plasmin.
- Plg(-/-) mice showed decreased bone mineral density.
Conclusions:
- Plasminogen plays a crucial role in regulating osteoblast and osteoclast function.
- Disruption of the fibrinolytic system, specifically plasminogen deficiency, leads to impaired bone metabolism and reduced bone mineral density.
- Targeting the plasminogen/plasmin system offers potential therapeutic strategies for bone diseases.
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...
01:40Bone 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.
01:17Hormones 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...
01:29Bone Disorders
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:23Role of Matrix Metalloproteases in Degradation of ECM
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
A...
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...