Related Experiment Video

Updated: Jul 2, 2025

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
08:42

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

4.4K

Crosstalk between ALK3(BMPR1A) deficiency and autophagy signaling mitigates pathological bone loss in osteoporosis

Zhixing Niu1, Yumeng Zhou2, Muchun Liang2

  • 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Bone
|February 26, 2024
PubMed

Insights

Bone morphogenetic protein receptor 1A (BMPR1A) plays a dual role in osteoporosis. Its deficiency initially reduces bone loss but impairs later bone maturation by affecting mTOR-autophagy pathways.

Area of Science:

  • * Skeletal Biology and Disease
  • * Molecular and Cellular Biology
  • * Endocrinology

Background:

  • * Postmenopausal osteoporosis is a major skeletal disease linked to impaired bone formation.
  • * Bone morphogenetic protein (BMP) signaling is crucial for osteoblast development but its role in osteoporosis is unclear.
  • * BMPR1A is a key receptor in BMP signaling pathways.

Purpose of the Study:

  • * To investigate the pathological role of BMPR1A in osteoporosis.
  • * To elucidate the underlying molecular mechanisms of BMPR1A's function in osteoporotic bone.
  • * To explore potential therapeutic targets for osteoporosis.

Main Methods:

  • * Used a Col1a1-creER mouse model to knock down BMPR1A in osteoblasts.
  • * Analyzed bone loss, mineral adherence, and bone formation rates in vivo.
  • * Investigated pre-osteoblast proliferation and mineralization in vitro.
  • * Examined the involvement of the mTOR-autophagy pathway.

Main Results:

  • * BMPR1A knockdown in osteoblasts mitigated early osteoporosis-related bone loss in mice.
  • * However, BMPR1A deficiency led to defects in late bone maturation, reducing mineral adherence and bone formation rates.
  • * In vitro, BMPR1A deficiency enhanced pre-osteoblast proliferation but impaired mineralization under osteoporotic conditions.
  • * BMPR1A deficiency triggered mTOR-autophagy pathway perturbation, enhancing transient proliferation but hindering final mineralization.

Conclusions:

  • * BMPR1A acts as a double-edged sword in osteoporotic bone formation.
  • * The BMPR1A-mTOR/autophagy axis is significant in regulating osteoblast function during osteoporosis.
  • * This study provides novel insights for developing therapeutic strategies for osteoporosis.
Keywords:
AutophagyBMPR1AOsteoblastsOsteoporosisProliferation

More Related Videos

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

13.2K
Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines06:00

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines

Published on: September 13, 2017

7.1K

Related Concept Videos

Osteoclasts in Bone Remodeling01:31

Osteoclasts 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...
2.9K
Bone Remodeling01:40

Bone 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.
38.3K
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...
3.8K
Bone Disorders01:29

Bone 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...
3.5K
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...
3.6K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K