Related Experiment Video
Updated: Sep 12, 2025
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
11.8K
Unravelling Osteoporosis: Key Genes and Potential Therapies
Huichao Fu1, Yunjiao Wu2, Hongfei Lv1
1Department of Orthopedic Surgery, Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Journal of Cellular and Molecular Medicine
|August 6, 2025
Summary
This study identifies FMO4, PSMA4, and VEGFA as key genes linked to osteoporosis risk. These findings offer potential new therapeutic targets for metabolic bone disease treatment.
Area of Science:
- Genetics and Molecular Biology
- Immunology
- Pharmacology
Background:
- Osteoporosis is a prevalent metabolic bone disease causing decreased bone mass and increased fracture risk, particularly in aging women.
- Existing osteoporosis treatments have limitations and side effects, necessitating the identification of novel therapeutic targets.
Purpose of the Study:
- To identify druggable genes associated with osteoporosis using Mendelian randomization (MR) and GWAS data.
- To explore the molecular mechanisms, immune relevance, and signalling pathways of identified osteoporosis-associated genes.
- To suggest potential therapeutic compounds for osteoporosis based on identified gene targets.
Main Methods:
- Mendelian randomization (MR) analysis on GWAS data from the FinnGen consortium.
- Transcriptomic profiling, single-cell RNA sequencing (scRNA-seq), and immune infiltration analysis.
- Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) to investigate signalling pathways.
Main Results:
- Three genes—FMO4, PSMA4, and VEGFA—were significantly associated with osteoporosis risk.
- FMO4 demonstrated a protective association, enriched in vascular and immune cells.
- PSMA4 was upregulated in macrophages and T cells, potentially affecting bone remodelling via immune-related protein degradation.
- VEGFA expression positively correlated with osteoporosis risk, possibly through ER-β-mediated signalling promoting osteoblast apoptosis.
- Identified genes are involved in calcium signalling, Wnt/β-catenin, PI3K/Akt, and Hedgehog signalling pathways.
- Immune analysis revealed strong associations with dendritic cells and macrophages.
- Identified 52 candidate compounds for VEGFA and 8 for PSMA4.
Conclusions:
- FMO4, PSMA4, and VEGFA are key genes implicated in osteoporosis pathogenesis.
- These genes are linked to critical signalling pathways and immune cell interactions relevant to bone metabolism.
- The study provides a foundation for developing novel osteoporosis therapeutics targeting these genes and associated pathways.
Related Concept Videos
01:17Hormones and Bone Tissue
2.9K
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...
2.9K
01:29Bone Disorders
3.9K
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...
3.9K
01:31Osteoclasts in Bone Remodeling
3.2K
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...
3.2K
01:40Bone Remodeling
38.5K
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.
38.5K
01:25Role of Vitamins in Maintaining Bone Health
3.7K
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...
3.7K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.8K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.8K