Autophagy Mechanisms in Bone Metabolism Disorders

The skeletal system is sustained by a dynamic equilibrium between bone formation and resorption, orchestrated by osteoblasts, osteoclasts and osteocytes. Autophagy, a lysosome-dependent degradation pathway, has emerged as a pivotal regulator of bone cell homeostasis and survival in metabolic disorders such as osteoporosis, diabetes-associated bone fragility and age-related bone loss. By eliminating damaged organelles and protein aggregates, autophagy modulates the differentiation, activity and longevity of bone marrow mesenchymal stem cells (MSCs), osteoblasts and osteocytes. Dysregulated autophagic flux disrupts the balance between bone matrix deposition and resorption, leading to impaired regeneration, microarchitectural deterioration and reduced bone mineral density. Elucidating how autophagy and its selective variant mitophagy influence cellular energy management and stress responses in bone tissues is essential for the development of targeted therapies to restore skeletal integrity in metabolic bone diseases.

Research from Nature Portfolio

Studies have shown that enhancing autophagy in osteoblasts via activation of SIRT1 restores bone quality in oestrogen-deficient models by upregulating LC3 and Beclin-1 while inhibiting PI3K/AKT/mTOR signalling. Complementary work using osteoblast-lineage-specific deletion of the autophagy gene Atg7 demonstrated profound reductions in trabecular bone mass and alterations in osteocyte canalicular networks. Together, these investigations underline the essential role of canonical autophagy pathways in driving osteoblast maturation, maintaining osteocyte connectivity and preserving overall skeletal homeostasis.

Autophagy Mechanisms in Bone Metabolism Disorders publication trend

The graph below shows the total number of articles in autophagy mechanisms in bone metabolism disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Autophagy: Evolutionarily conserved process for lysosomal degradation of cellular components to maintain homeostasis and energy balance.

Mitophagy: Selective autophagic clearance of damaged or superfluous mitochondria to ensure mitochondrial quality control.

Mesenchymal Stem Cell (MSC): Multipotent progenitor of the bone marrow capable of differentiating into osteoblasts, chondrocytes and adipocytes.

Osteoblast: Bone-forming cell that synthesises and mineralises the organic matrix of bone.

Osteocyte: Mechanosensitive cell derived from osteoblasts, embedded in bone matrix and regulating remodelling.

Osteoclast: Multinucleated cell responsible for bone matrix resorption during remodelling.

References

1. WAC Facilitates Mitophagy‐mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination‐Dependent Degradation. Advanced Science (2024).
2. PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products. Cell Death & Disease (2023).
3. The Role and Mechanism of SIRT1 in Resveratrol-regulated Osteoblast Autophagy in Osteoporosis Rats. Scientific Reports (2019).
4. Low bone mass and changes in the osteocyte network in mice lacking autophagy in the osteoblast lineage. Scientific Reports (2016).