Broken Bones and Beyond

Reut Shainer ¹ Vardit Kram ¹ Tina M. Kilts ¹ Li Li ¹ Carl G. Simon Jr ² Andrew Doyle ³ Lilana Schaefer ⁴ Marian F. Young ¹

¹Molecular Biology of Bones and Teeth Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
²Biosystems and Biomaterials Division, National Institute of Standards and Technology, USA
³Cell Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA
⁴Institut für Allgemeine Pharmakologie und Toxikologie, Goethe University, Germany

Bone regeneration involves complex sequences of physiological events starting with an inflammatory response that is necessary for early stages of bone healing and subsequent activation of skeletal stem cells in the periosteum. To identify new factors that further control periosteal cell function, immunohistochemistry was performed and showed that Biglycan (Bgn), a matrix proteoglycan, is greatly enhanced in the periosteum in response to injury. Considering the numerous abnormalities we found in the Bgn KO bones, we established a new fracture technique and tested their healing ability. Interestingly, Bgn deficient (KO) mice subjected to induced fracture have a reduced inflammatory response accompanied by a decreased expansion of the periosteal layer and, ultimately, impaired callus formation and collagen organization, compared with WT bones. Using a 3D system to mimic the native environment of the cells we found that periosteal cells create distinct microenvironment that favors cartilage formation. In Vivo Transplantion of the periosteal cells on the 3D system further influenced the healing process.

Overall, our results highlight the importance of the extracellular matrix component Bgn in the periosteum during bone healing and in regulating bone integrity.