Related Experiment Video
Updated: Aug 17, 2025
08:42
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
4.5K
Regulation of bone homeostasis by MERTK and TYRO3
Janik Engelmann1,2,3,4,5, Jennifer Zarrer6,7,8, Victoria Gensch1,2,3,4,5
1Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nature Communications
|December 12, 2022
Summary
Targeting TAM receptors MERTK and TYRO3 in osteoblasts impacts bone mass. Blocking MERTK with R992 promotes bone formation and counters cancer-induced bone loss, offering potential osteoanabolic therapy.
Area of Science:
- Bone biology and homeostasis
- Cancer-induced bone loss
- TAM receptor signaling
Background:
- Bone homeostasis relies on osteoblasts and osteoclasts.
- TAM receptors MERTK and TYRO3 influence osteoblast function.
- Dysregulation contributes to bone diseases and cancer complications.
Purpose of the Study:
- Investigate the reciprocal roles of MERTK and TYRO3 in osteoblast biology.
- Elucidate the molecular mechanisms underlying their effects.
- Evaluate MERTK blockade as a therapeutic strategy for bone loss and cancer.
Main Methods:
- Osteoblast-specific gene deletion of MERTK and TYRO3 in mice.
- Pharmacologic MERTK inhibition using R992.
- Assessment of bone mass, osteoblast differentiation, and cancer models.
Main Results:
- MERTK deletion increased bone mass; TYRO3 deletion decreased it.
- MERTK signaling negatively regulates osteoblast differentiation via the VAV2-RHOA-ROCK axis.
- R992 treatment enhanced bone formation and reduced cancer-related bone loss and metastasis.
Conclusions:
- MERTK and TYRO3 are key regulators of bone homeostasis with opposing functions.
- MERTK blockade with R992 demonstrates osteoanabolic potential.
- MERTK inhibition is a promising therapeutic avenue for bone disorders and cancer treatment.
More Related Videos
Related Concept Videos
01:40Bone Remodeling
38.4K
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.
38.4K
01:31Osteoclasts in Bone Remodeling
3.1K
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...
3.1K
01:17Hormones and Bone Tissue
2.8K
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...
2.8K
01:15Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
01:21Skeleton and Calcium Homeostasis
4.7K
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.
4.7K
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K