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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 bone...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Bone Remodeling and Repair01:31

Bone Remodeling and Repair

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 bone...
Hormones and Bone Tissue01:17

Hormones 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...
Essential Minerals for Bone Health01:31

Essential Minerals for Bone Health

The minerals contained in all of the food we consume are essential for our organ systems. However, certain essential minerals, such as calcium, phosphorus, magnesium, manganese, and fluoride, largely affect bone health.
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Calcium is a critical component of bones, especially in the form of calcium phosphate and calcium carbonate. Since the body cannot make calcium, it must be obtained from the diet. However, calcium cannot be absorbed from the small intestine without...

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Related Experiment Videos

Hydroxygenkwanin exerts osteoprotective effects by regulating LRG1-PJA1-PML axis.

Xiaoxiao Wu1, Lu Liu2, Sihang Fan3

  • 1The First Affiliated Hospital, Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian 116011, China; Department of Orthopedics, Taihe Hospital, Hubei University of Medicine, No.32, RenminSouth Road, Maojian District, Shiyan 442000, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|June 16, 2026
PubMed
Summary

Hydroxygenkwanin (HGK), a natural compound, combats osteoporosis by stabilizing the osteogenic regulator promyelocytic leukemia protein (PML). This novel approach targets the LRG1-PJA1-PML axis, offering a potential new therapy for bone loss.

Keywords:
HydroxygenkwaninLRG1OsteoporosisPJA1PML ubiquitination

Related Experiment Videos

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Osteoporosis poses a significant public health challenge, particularly postmenopausal osteoporosis, due to increased fracture risk.
  • Existing osteoporosis treatments have limitations including adverse effects and high costs, driving the search for safer alternatives.
  • Natural compounds are being explored for their therapeutic potential in managing osteoporosis.

Purpose of the Study:

  • To identify novel osteoprotective compounds and elucidate their mechanisms of action.
  • To investigate the potential of hydroxygenkwanin (HGK), a flavonoid from Daphne genkwa, as a therapeutic agent for osteoporosis.
  • To uncover the molecular pathway targeted by HGK in bone metabolism.

Main Methods:

  • Ovariectomized (OVX) mouse model to study osteoporosis.
  • Femoral RNA sequencing to identify differentially expressed genes.
  • Bioinformatics analysis and co-immunoprecipitation assays to identify protein interactions.
  • In vivo studies to assess bone loss and microarchitecture.
  • Biochemical assays (CETSA, pull-down) and molecular dynamics simulations to validate molecular interactions.

Main Results:

  • HGK treatment significantly attenuated OVX-induced bone loss and improved bone microarchitecture in mice.
  • HGK was found to directly bind to leucine-rich alpha-2-glycoprotein 1 (LRG1).
  • HGK promotes the stabilization of promyelocytic leukemia protein (PML) by modulating the LRG1-PJA1-PML axis, thereby enhancing osteoblast differentiation.

Conclusions:

  • Hydroxygenkwanin (HGK) is a potent osteoprotective compound with a novel mechanism of action.
  • The LRG1-PJA1-PML axis is a critical pathway in osteoporosis.
  • HGK represents a first-in-class therapeutic candidate for osteoporosis by targeting this pathway.