Related Experiment Video

Updated: Jul 7, 2026

Chondrogenic Differentiation Induction of Adipose-derived Stem Cells by Centrifugal Gravity
08:30

Chondrogenic Differentiation Induction of Adipose-derived Stem Cells by Centrifugal Gravity

Published on: February 24, 2017

mTOR signaling contributes to chondrocyte differentiation

Chanika Phornphutkul1, Ke-Ying Wu, Valerie Auyeung

  • 1Department of Pediatrics, Division of Pediatric Endocrinology and Metabolism, Rhode Island Hospital and Brown University, Providence, Rhode Island 02903, USA. chanika_phornphutkul@brown.edu

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|February 12, 2008
PubMed

Insights

Nutrient sensing via the mammalian Target Of Rapamycin (mTOR) pathway regulates chondrocyte differentiation and long bone growth. Inhibiting mTOR with rapamycin specifically impacts hypertrophic chondrocytes, affecting growth and differentiation markers.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Biochemistry

Background:

  • The mammalian Target Of Rapamycin (mTOR) is a key nutrient-sensing kinase regulating cellular functions.
  • Chondrogenesis, the process of cartilage formation, is crucial for long bone development.
  • Understanding nutrient-mediated regulation of chondrogenesis is vital for skeletal biology.

Purpose of the Study:

  • To investigate the role of mTOR signaling in chondrogenesis using fetal rat metatarsal explants and an in situ model.
  • To determine the specific effects of mTOR inhibition on chondrocyte proliferation, differentiation, and key molecular markers.

Main Methods:

  • Utilized fetal rat metatarsal explants and in situ injections of rapamycin (mTOR inhibitor) in embryonic day 19 rats.
  • Assessed cell proliferation via bromodeoxyuridine incorporation.
  • Analyzed proteoglycan accumulation, collagen X expression, and Indian Hedgehog (Ihh) levels in the ATDC5 chondrogenic cell line.

Main Results:

  • mTOR inhibition by rapamycin diminished insulin-stimulated growth in metatarsal explants, primarily affecting the hypertrophic zone.
  • Rapamycin did not alter cell proliferation but inhibited proteoglycan and collagen X expression in ATDC5 cells.
  • Rapamycin decreased Indian Hedgehog (Ihh) levels, an effect reversed by Ihh addition.

Conclusions:

  • mTOR signaling modulates chondrocyte differentiation, potentially via regulation of Indian Hedgehog (Ihh).
  • Nutrients, acting through mTOR, directly influence chondrocyte differentiation and long bone growth.
  • These findings highlight mTOR as a critical regulator in skeletal development.

More Related Videos

Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification07:23

Culture of Murine Embryonic Metatarsals: A Physiological Model of Endochondral Ossification

Published on: December 3, 2016

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR 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...
mTOR Signaling and Cancer Progression03:03

mTOR 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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Growth of Cartilage and Bone Tissue01:27

Growth of Cartilage and Bone Tissue

Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...