Osteocytes
Living inside the stone
Credit: Art by Nelli Aghekyan, Set in motion by Dr. Emanuele Petretto. Words by Dr. Masia Maksymowicz, Project Coordinator: Dr. Masia Maksymowicz, Series Director: Dr. Radhika Patnala
#Extraordinarycelltypes #sciart #lifescience
Living among the dead
When we think of the words skeleton or bones, the first associations that most of us will have are strength, hardness, stone-like, and maybe even dead. Yet, if we look closer, a single bone of our skeleton contains inside it cells, osteocytes, which are surrounded by the stone-like mineral structure called bone matrix. Osteocytes are derived from osteoblasts, cells responsible for the formation of bone tissue, by synthesizing and secreting bone matrix and participating in the bone mineralization (1). In turn, osteocytes are the cells present inside the fully formed bone.
Wood grains inside our bones
Osteocytes make up 90–95% of bone cells (2). Their main function is sensing mechanical stress and strain on bones, thus helping to regulate bone density and strength in response to mechanical forces. They also play a role in mineral metabolism, influencing the deposition and resorption of minerals such as calcium and phosphate in bone tissue. All these functions require being able to communicate with other cells and their surroundings, thus osteocytes have a unique shape. Their cell body is located inside a small space called lacuna, while the dendritic processes reside in tiny cylindrical channels called canaliculi (~ 250–300 nm in diameter) (3). Thanks to these lacunae and canaliculi, when we cut the bone in half, we will see something similar to wood grains.
The way to such a shape is not a simple one though. Their precursors, osteoblasts, are big and capable of production of collagen, a very big, most abundant protein in the human body. On the other hand, osteocytes are smaller and dendrite-like, and, unlike osteoblasts, don’t have polarized structure (4). Thus, the differentiation from one to another requires many changes in the intracellular structure, which however are not well characterized yet (2).
Endocrine function of osteocytes
Osteocytes are long-lived and can survive for decades within the bone matrix (5). Thus, it is even more important that they keep communicating with their surroundings. Firstly, they can modify the surrounding bone tissue, by removing and replacing calcium and phosphate. Secondly, increased levels of phosphate and calcium are recognised by several organs in the body (6). As such, osteocytes participate in endocrine signalling, controlling phosphate reabsorption in the kidney, insulin secretion in the pancreas, and skeletal muscle function (6). Thirdly, osteocytes communicate with shorter-lived osteoblasts and osteoclasts. For that, they use direct, cell-to-cell communication via gap junctions, as well as intracellular signalling pathways (e.g. RANKL and Wnt) (6,7).
Osteocytes in osteoporosis and cancer bone metastasis
While signalling and intracellular communication between bone cells are still the main focus of research on osteocytes, some topics seem especially exciting. First of all, it is known that disruptions in the function of osteocytes can contribute to bone diseases such as osteoporosis. This disease is especially common among postmenopausal women and is linked to estrogen deficiency (8). Osteocytes are involved in bone ageing, another factor related to osteoporosis. Aged osteocytes have degenerated lacuna-canalicular networks, as well as impaired mechanosensitivity and remodeling signalling (9). Interestingly, the impairment of the osteocytic networks is also observed in cancer metastases present inside the bones (10). Studies suggest that cancer cells, by changing the intracellular signalling, can alter the bone structure and lacunar-canalicular network, caused by the apoptosis of osteocytes (10). However, osteocytes are also protecting bones from cancer growth. It was shown that by transferring their mitochondria to cancer cells, osteocytes activate anti-tumor response, which could be used to block bone metastasis (11).
Recognizing and appreciating the labs working in this space
- Dr Stefaan Verbruggen, Queen Mary University of London, London, UK, https://stefaanverbruggen.com/ , Twitter: @DocBruggsBunny
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Italy. Website: https://discab.univaq.it/index.php?id=1596 . Twitter: @univaq
- Lewis Laboratory, Cornell University, New York, USA. Website: https://www.kjlewislab.com/ , Twitter: @The_Lewis_Lab
- Skeletal Mechanobiology and Biomechanics Lab, Boston University, USA. Twitter: @MorganLabBU
- Schaffler Lab, Biomedical Engineering department, The City University of New York, USA. Twitter: @SchafflerLab
- Laboratory for Bone Biomechanics, ETH Zurich, Switzerland, https://www.bone.ethz.ch/
- Delgado-Calle Lab, UAMS College of Medicine, Arkansas, USA, https://medicine.uams.edu/physiology/faculty/primary-faculty/jesus-delgado-calle-ph-d/delgado-calle-lab/
- Boerckel Lab, University of Pennsylvania, Philadelphia, USA, https://www.med.upenn.edu/orl/boerckellab/ , Twitter: @jboerckel
- Basic Science Laboratory, University of Tennessee, Memphis, USA, https://www.uthsc.edu/nephrology/research/bsl/index.php
- Onal Lab, UAMS College of Medicine, Arkansas, USA, https://medicine.uams.edu/physiology/faculty/primary-faculty/melda-onal/onal-lab/
References
- Ponzetti, Marco, and Nadia Rucci. “Osteoblast Differentiation and Signaling: Established Concepts and Emerging Topics.” International journal of molecular sciences vol. 22,13 6651. 22 Jun. 2021, doi:10.3390/ijms22136651
- Schaffler, Mitchell B, and Oran D Kennedy. “Osteocyte signaling in bone.” Current osteoporosis reports vol. 10,2 (2012): 118–25. doi:10.1007/s11914–012–0105–4
- Bonewald L. Osteocytes. In: Marcus R, editor. Osteoporosis. 3rd. Elsevier; 2008. pp. 170–189.
- Gu, Guoliang et al. “Isolated primary osteocytes express functional gap junctions in vitro.” Cell and tissue research vol. 323,2 (2006): 263–71. doi:10.1007/s00441–005–0066–3
- Manolagas, S C. “Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis.” Endocrine reviews vol. 21,2 (2000): 115–37. doi:10.1210/edrv.21.2.0395
- Robling, Alexander G, and Lynda F Bonewald. “The Osteocyte: New Insights.” Annual review of physiology vol. 82 (2020): 485–506. doi:10.1146/annurev-physiol-021119–034332
- Civitelli, Roberto. “Cell-cell communication in the osteoblast/osteocyte lineage.” Archives of biochemistry and biophysics vol. 473,2 (2008): 188–92. doi:10.1016/j.abb.2008.04.005
- Cheng, Chu-Han et al. “Osteoporosis Due to Hormone Imbalance: An Overview of the Effects of Estrogen Deficiency and Glucocorticoid Overuse on Bone Turnover.” International journal of molecular sciences vol. 23,3 1376. 25 Jan. 2022, doi:10.3390/ijms23031376
- Cui, Jiarui et al. “Osteocytes in bone aging: Advances, challenges, and future perspectives.” Ageing research reviews vol. 77 (2022): 101608. doi:10.1016/j.arr.2022.101608
- Verbruggen, Stefaan W. “Role of the osteocyte in bone metastasis — The importance of networking.” Journal of bone oncology vol. 44 100526. 17 Jan. 2024, doi:10.1016/j.jbo.2024.100526
- Zhou, Hao et al. “Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity.” Science advances vol. 10,3 (2024): eadi4298. doi:10.1126/sciadv.adi4298
About the author:
DR. MAŁGORZATA ‘MASIA’ MAKSYMOWICZ
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Maksymowicz did her Ph.D. in Cell Biology (IIMCB, Poland) studying the intracellular trafficking and inflammatory signalling of a cytokine receptor. She did a 1-year post-doc at Nencki Institute, Poland, studying the protein- and RNA-binding properties of proteins. Currently, she is doing a post-doc at Barts Cancer Institute, UK, studying the links between endocytosis and tumorigenesis. Dr. Maksymowicz is passionate about science and loves to combine different fields of biology, always trying to seek beauty in nature.
About the artist:
NELLY AGHEKYAN
Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories
Nelli Aghekyan, did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
