ArticleThe Journal of biological chemistry2015
Inhibition of osteocyte apoptosis prevents the increase in osteocytic receptor activator of nuclear factor κB ligand (RANKL) but does not stop bone resorption or the loss of bone induced by unloading.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 86 citations in OpenAlex.
- The emerging role of subchondral bone homeostasis in osteoarthritis.Journal of orthopaedic translation · 2026Review
- Extracellular vesicles in osteoarthritis: pathological mechanisms, regenerative therapies and clinical translation.Stem cell research & therapy · 2026Review
- Bone tissue regeneration: role of osteocyte mechanosensing and mechanotransduction.Stem cells translational medicine · 2026Review
- A Novel Concept of Tissue Micro-Instability as the Underlying Mechanism of Osteophytosis in Human Knee Osteoarthritis.Biomedicines · 2026Article
- CAV-1 regulates osteocyte communication with osteoclast and osteoblast precursors.Scientific reports · 2025Article
- [Pathology of Cartilage-to-Bone Crosstalk: A New Angle for Animal Experimental Studies on Osteoarthritis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Review
- Articular cartilage degeneration and aberrant osteocyte perilacunar/canalicular remodeling in subchondral bone of patients with developmental dysplasia of the hip.BMC musculoskeletal disorders · 2025Article
- From death to birth: how osteocyte death promotes osteoclast formation.Frontiers in immunology · 2025Review
- Osteoporosis, Osteoarthritis, and Subchondral Insufficiency Fracture: Recent Insights.Biomedicines · 2024Review
- Transient receptor potential vanilloid 1: A potential therapeutic target for the treatment of osteoarthritis and rheumatoid arthritis.Cell proliferation · 2024Review
- Effects of Weight Bearing on Marrow Adipose Tissue and Trabecular Bone after Anterior Cruciate Ligament Reconstruction in the Rat Proximal Tibial Epiphysis.Acta histochemica et cytochemica · 2024Article
- Microenvironmental interference with intra-articular stem cell regeneration influences the onset and progression of arthritis.Frontiers in genetics · 2024Review
- Novel role for alpha-2-macroglobulin (A2M) as a disease modifying protein in senile osteoporosis.Frontiers in cell and developmental biology · 2023Article
- Pathways Controlling Formation and Maintenance of the Osteocyte Dendrite Network.Current osteoporosis reports · 2022Review
- PTH1R translocation to primary cilia in mechanically-stimulated ostecytes prevents osteoclast formation via regulation of CXCL5 and IL-6 secretion.Journal of cellular physiology · 2022Article
- Damaged Mesenchymal Cells Dampen the Inflammatory Response of Macrophages and the Formation of Osteoclasts.Journal of clinical medicine · 2022Article
- Disuse Osteoporosis: Clinical and Mechanistic Insights.Calcified tissue international · 2022Review
- RANKL Blockade Reduces Cachexia and Bone Loss Induced by Non-Metastatic Ovarian Cancer in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Senescent skeletal cells cross-talk with synovial cells plays a key role in the pathogenesis of osteoarthritis.Arthritis research & therapy · 2022Review
- The osteocyte as a signaling cell.Physiological reviews · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Apoptosis of osteocytes and osteoblasts precedes bone resorption and bone loss with reduced mechanical stimulation, and receptor activator of NF-κB ligand (RANKL) expression is increased with unloading in mice. Because osteocytes are major RANKL producers, we hypothesized that apoptotic osteocytes signal to neighboring osteocytes to increase RANKL expression, which, in turn, increases osteoclastogenesis and bone resorption. The traditional bisphosphonate (BP) alendronate (Aln) or IG9402, a BP analog that does not inhibit resorption, prevented the increase in osteocyte apoptosis and osteocytic RANKL expression. The BPs also inhibited osteoblast apoptosis but did not prevent the increase in osteoblastic RANKL. Unloaded mice exhibited high serum levels of the bone resorption marker C-telopeptide fragments of type I collagen (CTX), elevated osteoclastogenesis, and increased osteoclasts in bone. Aln, but not IG9402, prevented all of these effects. In addition, Aln prevented the reduction in spinal and femoral bone mineral density, spinal bone volume/tissue volume, trabecular thickness, mechanical strength, and material strength induced by unloading. Although IG9402 did not prevent the loss of bone mass, it partially prevented the loss of strength, suggesting a contribution of osteocyte viability to strength independent of bone mass. These results demonstrate that osteocyte apoptosis leads to increased osteocytic RANKL. However, blockade of these events is not sufficient to restrain osteoclast formation, inhibit resorption, or stop bone loss induced by skeletal unloading.
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