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Rethinking the Importance of Bone Cells: What’s in an Osteocyte with Dr. Lynda Bonewald

Rethinking the Importance of Bone Cells

“Bone is essential for maintaining the health of the organism.”

Dr Lynda Bonewald addressed questions regarding the broader impact of her research with these words. For the better part of her career, Dr Bonewald has gleaned a deeper understanding of the osteocyte, a cell long considered dormant, inactive, and ‘a placeholder’ in bone tissue. Most well known as being retired osteoblasts (bone building cells), osteocytes are indeed bone-embedded and osteoblast-derived, but Dr Bonewald contests they are more important than imagined.

Only recently was the complexity of the osteocyte network even described. These cells grow out in the bone space, interacting with ion signals through long dendritic processes, creating a fascinating system of intercellular connections. These cells interact not only with each other but also with vasculature, osteoblasts, osteoclasts, and marrow cells. It has long been argued such a network simply must have a function, and while this is now almost undeniably true the full extent of its purpose remains an area of much investigation.

This figure from Dallas et al.'s 2013 review "The Osteocyte: An Endocrine Cell...and More" shows the broad reach of osteocytes in mineralized bone tissue.

This figure from Dallas et al.’s 2013 review “The Osteocyte: An Endocrine Cell…and More” shows the broad reach of osteocytes in mineralized bone tissue.

Dr Bonewald’s 2011 review in the Journal of Bone and Mineral Research, “The Amazing Osteocyte”, describes just a handful of the proven roles osteocytes play not just in bone health and homeostasis, but also their role in a much broader signaling network.

  • Osteocytes not only possess potential to activate osteoblasts, but also osteoclasts, essentially regulating both sides of the bone anabolism/catabolism balance.\
  • Osteocyte death leads to inflammation and bone fragility.
  • Wnt/b-catenin regulate osteocyte function (whereas previously osteocytes hadn’t been considered important in bone regulation).
  • Osteocytes are a source of minerals and factors, like Calcium, FGF-23, and Dmp1, which signal not just to other bone cells but in an endocrine fashion to many other organs.
  • Osteocytes play a mechanosensory role. The dendritic network of osteocytes allows communication across large areas of bone, and these cells are subject to all the stress and strains of the bone matrix itself.
Again from Dallas et al. the figure demonstrates how osteocytes interact with both osteoblasts and osteoclasts, and their influence is greater than previously thought.

Again from Dallas et al. the figure demonstrates how osteocytes interact with both osteoblasts and osteoclasts, and their influence is greater than previously thought.

In her talk at the Hospital for Special Surgery, October 26, 2015, Dr Bonewald spoke specifically about osteocyte remodeling and parathyroid hormone (PTH)’s function.   PTH is important for increasing bone mass, and it does so through increasing osteoblastic markers in osteocytes, essentially causing a reversion to an osteoblastic phenotype. Strikingly, PTH caused a notable increase in osteocyte motility (likely in early osteocytes and not fully embedded cells).

Focus was also drawn to the perilacunar matrix which surrounds the osteocytes embedded in bone (outside the lacuna, or space in bone which the cell inhabits). This space may be remodeled far more than previously expected, and it may be an extracellular reserve of calcium and other signaling factors. Dr Bonewald noted changes in the size of this perilacunar space during lactation, supporting a theory of PTH-regulated osteocyte activity which involves decreasing local matrix collagen as well as a drop in pH. This all leads to compromised bone and dissolution of matrix; in turn, the osteocyte becomes an interesting new therapeutic target to consider.

As Dr Bonewald points out, the surface area presented by the osteocyte network with their dendrites far exceeds Haversian canal area or even trabecular area, and the volume of the osteocyte cytoplasmic space may even rival the volume of the brain. Such a complex system with so many acting partners likely plays an even more important and complicated role than we know in spite of a full career defining the osteocyte.

The figure above from the Dallas review displays how bone may regulate many other organ systems through, for example, osteocyte produced factor FGF23.

The figure above from the Dallas review displays how bone may regulate many other organ systems through, for example, osteocyte produced factor FGF23.

Ultimately a cell which can live to ages tens of years longer than other cells, embedded in a tissue that is not considered very dynamic, has long held many secrets to bone homeostasis as well as numerous systemic functions. From where the field started, with the first occasional reference to cells called osteocytes in the 1940s, the complexity of questions has grown tremendously as has the quality and integrity of research and availability of technology, and this is in no small part a direct result of the career of Dr Lynda Bonewald.

References:
Dallas et al. 2013
Bonewald et al. 2011

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