Related Experiment Video
Updated: Jul 11, 2026
07:23
Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification
Published on: December 3, 2016
Cellular mechanisms for methotrexate chemotherapy-induced bone growth defects
Cory J Xian1, Johanna C Cool, Michaela A Scherer
1Department of Orthopaedic Surgery, Women's and Children's Hospital, Adelaide, South Australia; Discipline of Paediatrics, University of Adelaide, Australia. cory.xian@adelaide.edu.au
Bone
|September 22, 2007
Summary
Methotrexate (MTX) chemotherapy causes temporary bone growth defects in young rats by damaging growth plate cells and reducing bone formation. Recovery was observed within 21 days.
Area of Science:
- Pediatric Oncology
- Bone Biology
- Chemotherapy Effects
Background:
- Methotrexate (MTX) is a vital anti-metabolite in pediatric cancer treatment.
- MTX is associated with bone growth arrest and osteoporosis, but mechanisms are unclear.
Purpose of the Study:
- To investigate the cellular mechanisms of MTX-induced bone growth defects in young rats.
- To characterize the effects of acute MTX chemotherapy on growth plate and metaphyseal bone cells.
Main Methods:
- Young rats received 5 daily doses of MTX (0.75 mg/kg).
- Cellular activities, including proliferation and apoptosis, were assessed in the growth plate and metaphysis.
- Histological analysis of growth plate and trabecular bone was performed at various time points.
Main Results:
- MTX induced significant chondrocyte apoptosis and suppressed proliferation, reducing growth plate thickness and collagen-II expression.
- Bone formation in the metaphysis was reduced, with decreased primary spongiosa and secondary spongiosa bone volume.
- Osteocyte apoptosis and reduced osteoblast proliferation were observed in the metaphysis.
- Most cellular and histological parameters recovered by day 14-21.
Conclusions:
- MTX chemotherapy can impair bone growth by disrupting cellular activities in the growth plate and reducing osteoblastic cell populations.
- Short-term MTX treatment results in transient bone growth suppression, with significant recovery observed.
- These findings provide insights into the mechanisms of MTX-induced bone toxicity in pediatric oncology.
Related Concept Videos
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...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
03:03mTOR Signaling and Cancer Progression
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...
03:03mTOR Signaling and Cancer Progression
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...
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
01:10Drugs that Destabilize Microtubules
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...