Oral and Craniofacial Sciences Faculty

Lynda Bonewald, Ph.D




















Dr. Bonewald’s research has focused on osteocyte biology since 1996 beginning with the establishment of an osteocyte-like cell line, MLO-Y4 (Journal of Bone and Mineral Research, JBMR 1999), a late osteoblast, early osteocyte cell line, MLO-A5 (JBMR 2001) and more recently, a cell line that replicates late osteoblast to late osteocytes, IDG-SW3 (JBMR 2011).  Osteocytes are the most abundant bone cell in the adult skeleton.  In the last decade, it has been determined that these cells are multifunctional including 1).  Acting as orchestrators to regulate bone remodeling through direct actions on both osteoblasts and osteoclasts, 2). As endocrine cells regulating distant organs such as kidney and muscle, 3). As mechanosensory cells determining bone response to loading and unloading, 4). As regulators of the mineralization process, and 5). Regulators of mineral homeostasis. (“Osteocytes as Multifunctional Cells”, J Mus Neu Interact 2006; “The Amazing Osteocyte, JBMR 2010).  At present she is studying osteoblast to osteocyte differentiation, the functions of the osteocyte during lactation, and the crosstalk between osteocytes and muscle.

Figure 1. The process of osteoblast to osteocyte differentiation. (A) Tetrachrome staining of murine cortical bone. The osteoid seam is demonstrated with light blue staining and the mineralized bone is stained black with Von Kossa. The stages of differentiation are described as follows: 1) A mature osteoblast on the surface of the osteoid. 2) An osteoid-osteocyte, which is embedded in the unmineralized osteoid. 3) A mineralizing osteocyte, which is partially surrounded by mineral. 4) A mineralizing osteocyte, completely surrounded by mineral. 5) A mature osteocyte, embedded deep within the mineralized ECM. (B) A schematic diagram showing the differentiation process outlined in (A) and the expression of known genes at each of these stages of differentiation. The numbers in brackets correspond to the numbers in (A). From: "The osteocyte: doing the hard work of the backstage” in "Bone: A Story Of Breakthroughs, A Promising Future". Medicographia, (N° 111)  (in press).


Figure 2. Osteocytes make contact with cells on the bone surface. The image is an acid-etched resin embedded murine bone visualized by scanning electron microscopy showing the high interconnectivity of the osteocyte lacuno-canalicular system. The top panel shows the fully resin-embedded marrow on the top and the complex osteocyte lacuno-canalicular network below where the mineral has been removed by acid etching. The bottom panel is a magnification showing canaliculi in contact with the bottom of a cell on the surface of the bone (arrow). From: Bonewald, LF: Osteocytes. In: Osteoporosis, Third Edition. R. Marcus, D. Feldman, D. Nelson, C. Rosen (eds). Third Ed. Elsevier Inc., Chap 8, 169-190, 2007.