ArticleCell proliferation2022
Substrate stiffness regulates the differentiation profile and functions of osteoclasts via cytoskeletal arrangement.
Article in Cell proliferation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Morphodynamic cellular changes prior to and during cell fusion related to osteoclast formation.Biochemistry and biophysics reports · 2026Article
- Macrophage polarization state influences fusion and phenotype of human foreign body giant cellsFrontiers in immunology · 2026Article
- Ciliary-Mediated Mechanotransduction in Skeletal Development and Diseases.Results and problems in cell differentiation · 2026Review
- How do mechanical forces impact macrophages in the processes of mechanosensing and mechanotransduction?Journal of Zhejiang University. Science. B · 2025Review
- The Effects and Mechanisms of Low-Intensity Pulsed Ultrasound on Bone Remodeling: From Laboratory to Clinic.Biomolecules · 2025Review
- Modeling the effects of radiation on the bone tumor microenvironment: opportunities for exploring combination therapies in microphysiologic systems.Cellular & molecular biology letters · 2025Review
- Mechanosignaling in Osteoporosis: When Cells Feel the Force.International journal of molecular sciences · 2025Review
- Modulation of Gene Expression by Substrate Stiffness via Ubiquitination of Histone H2B by Ubiquitin-Conjugating Enzyme E2A/B.ACS omega · 2025Article
- Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration.Advanced therapeutics · 2025Article
- Article
- Spectrin mediates 3D-specific matrix stress-relaxation response in neural stem cell lineage commitment.Science advances · 2024Article
- Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption.Science bulletin · 2024Article
- Mechanotransduction in subchondral bone microenvironment and targeted interventions for osteoarthritis.Mechanobiology in medicine · 2024Review
- Engineering approaches to manipulate osteoclast behavior for bone regeneration.Materials today. Bio · 2024Review
- Research progress on the regulatory mechanism of integrin-mediated mechanical stress in cells involved in bone metabolism.Journal of cellular and molecular medicine · 2024Review
- Biomaterial-based mechanical regulation facilitates scarless wound healing with functional skin appendage regeneration.Military Medical Research · 2024Review
- Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy.Journal of translational medicine · 2024Review
- [Research Progress in the Molecular Regulatory Mechanisms of Alveolar Bone Restoration].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- Osteoclastogenesis Requires Primary Cilia Disassembly and Can Be Inhibited by Promoting Primary Cilia Formation Pharmacologically.Cells, tissues, organs · 2024Article
- The age-related effects on orthodontic tooth movement and the surrounding periodontal environment.Frontiers in physiology · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectivesAging and common diseases alter the stiffness of bone tissue, causing changes to the microenvironment of the mechanosensitive bone cells. Osteoclasts, the sole bone-resorbing cells, play a vital role in bone remodeling. This study was performed to elucidate the mechanism through which osteoclasts sense and react to substrate stiffness signals. MATERIALS AND
methodsWe fabricated polydimethylsiloxane (PDMS) substrates of different stiffness degrees for osteoclast formation progressed from osteoclast precursors including bone marrow-derived macrophages (BMMs) and RAW264.7 monocytes. Osteoclast differentiation in response to the stiffness signals was determined by examining the cell morphology, fusion/fission activities, transcriptional profile, and resorption function. Cytoskeletal changes and mechanosensitive adhesion molecules were also assessed.
resultsStiffer PDMS substrates accelerated osteoclast differentiation, firstly observed by variations in their morphology and fusion/fission activities. Upregulation of canonical osteoclast markers (Nfatc1, Acp5, Ctsk, Camk2a, Mmp9, Rela, and Traf6) and the fusion master regulator DC-stamp were detected on stiffer substrates, with similar increases in their bone resorption functions. Additionally, the activation of cytoskeleton-associated adhesion molecules, including fibronectin and integrin αvβ3, followed by biochemical signaling cascades of paxillin, FAK, PKC, and RhoA, was detected on the stiffer substrates.
conclusionsThis is the first study to provide evidence proving that extracellular substrate stiffness is a strong determinant of osteoclast differentiation and functions. Higher stiffness upregulated the differentiation profile and activity of osteoclasts, revealing the mechanical regulation of osteoclast activity in bone homeostasis and diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.