ArticleFrontiers in endocrinology2014
A new method to investigate how mechanical loading of osteocytes controls osteoblasts.
Article in Frontiers in endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Frequency-Regulated Repeated Micro-Vibration Promotes Osteoblast Differentiation Through BMP Signaling in MC3T3-E1 Cells.Life (Basel, Switzerland) · 2025Article
- Study of Podoplanin-Deficient Mouse Bone with Mechanical Stress.Dentistry journal · 2025Article
- Using Cell and Organ Culture Models to Analyze Responses of Bone Cells to Mechanical Stimulation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Investigating mechanical and inflammatory pathological mechanisms in osteoarthritis using MSC-derived osteocyte-like cells in 3D.Frontiers in endocrinology · 2024Article
- A high-throughput biomimetic bone-on-a-chip platform with artificial intelligence-assisted image analysis for osteoporosis drug testing.Bioengineering & translational medicine · 2023Article
- Influence of Periodontal Ligament Stem Cell-Derived Conditioned Medium on Osteoblasts.Pharmaceutics · 2022Article
- The role of mechanobiology in bone and cartilage model systems in characterizing initiation and progression of osteoarthritis.APL bioengineering · 2022Review
- Peripheral Blood Mononuclear Cells (PBMCs) to Dissect the Underlying Mechanisms of Bone Disease in Chronic Kidney Disease and Rare Renal Diseases.Current osteoporosis reports · 2021Review
- Review
- Triple Culture of Primary Human Osteoblasts, Osteoclasts and Osteocytes as an In Vitro Bone Model.International journal of molecular sciences · 2021Article
- Multiomic analysis of stretched osteocytes reveals processes and signalling linked to bone regeneration and cancer.NPJ Regenerative medicine · 2021Article
- A Roadmap of In Vitro Models in Osteoarthritis: A Focus on Their Biological Relevance in Regenerative Medicine.Journal of clinical medicine · 2021Review
- Probing Osteocyte Functions in Gelatin Hydrogels with Tunable Viscoelasticity.Biomacromolecules · 2021Article
- Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons.Frontiers in cell and developmental biology · 2021Review
- A 3D, Dynamically Loaded Hydrogel Model of the Osteochondral Unit to Study Osteocyte Mechanobiology.Advanced healthcare materials · 2020Article
- Establishment ofExperimental and therapeutic medicine · 2020Article
- Comparative effectiveness of PEEK rods versus titanium alloy rods in cervical fusion in a new sheep model.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2020Article
- Therapeutic potentials and modulatory mechanisms of fatty acids in bone.Cell proliferation · 2020Review
- Strategy for achieving standardized bone models.Biotechnology and bioengineering · 2020Review
- In Vitro Co-culture Model of Primary Human Osteoblasts and Osteocytes in Collagen Gels.International journal of molecular sciences · 2019Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanical loading, a potent stimulator of bone formation, is governed by osteocyte regulation of osteoblasts. We developed a three-dimensional (3D) in vitro co-culture system to investigate the effect of loading on osteocyte-osteoblast interactions. MLO-Y4 cells were embedded in type I collagen gels and MC3T3-E1(14) or MG63 cells layered on top. Ethidium homodimer staining of 3D co-cultures showed 100% osteoblasts and 86% osteocytes were viable after 7 days. Microscopy revealed osteoblasts and osteocytes maintain their respective ovoid/pyriform and dendritic morphologies in 3D co-cultures. Reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) of messenger ribonucleic acid (mRNA) extracted separately from osteoblasts and osteocytes, showed that podoplanin (E11), osteocalcin, and runt-related transcription factor 2 mRNAs were expressed in both cell types. Type I collagen (Col1a1) mRNA expression was higher in osteoblasts (P < 0.001), whereas, alkaline phosphatase mRNA was higher in osteocytes (P = 0.001). Immunohistochemistry revealed osteoblasts and osteocytes express E11, type I pro-collagen, and connexin 43 proteins. In preliminary experiments to assess osteogenic responses, co-cultures were treated with human recombinant bone morphogenetic protein 2 (BMP-2) or mechanical loading using a custom built loading device. BMP-2 treatment significantly increased osteoblast Col1a1 mRNA synthesis (P = 0.031) in MLO-Y4/MG63 co-cultures after 5 days treatment. A 16-well silicone plate, loaded (5 min, 10 Hz, 2.5 N) to induce 4000-4500 με cyclic compression within gels increased prostaglandin E2 (PGE2) release 0.5 h post-load in MLO-Y4 cells pre-cultured in 3D collagen gels for 48, 72 h, or 7 days. Mechanical loading of 3D co-cultures increased type I pro-collagen release 1 and 5 days later. These methods reveal a new osteocyte-osteoblast co-culture model that may be useful for investigating mechanically induced osteocyte control of osteoblast bone formation.
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