Céline Colnot

Origins and functions of skeletal stem cells in bone regeneration

Céline Colnot
  • Anais Julien
  • Ester Martinez-Sarra
  • Stéphanie Pannier
  • Simon Perrin
  • Hadidja Mouigni
  • Elise Paniel

Origins and functions of skeletal stem cells in bone regeneration

Musculoskeletal disorders affect 1 in 7 people (10 million people in Europe) and are the second cause of disability worldwide. Fractures due to genetic diseases, osteoporosis or trauma have a prevalence of 1 in 50 people affected annually. Large bone defects caused by trauma, resection of bone tumors, osteonecrosis and severe skeletal dysplasia represent significant clinical challenges, as bone does not regenerate spontaneously in these situations. In order to enhance musculoskeletal regeneration, our research concentrates on the biology of skeletal stem cells that are the basis for the high regenerative capacities of skeletal tissues and that are potentially deficient in various musculoskeletal diseases and disorders. We aim to elucidate the mechanisms of stem cell activation in their complex tissue environment in development, disease and repair.

1-Role of skeletal stem cells

The process of bone formation begins during embryogenesis and continues throughout bone growth, homeostasis and aging, and during bone regeneration and repair. Many aspects of the developmental process are recapitulated during bone repair, including the differentiation of skeletal progenitors into osteoblasts and chondrocytes and the re-expression of genes involved in skeletal development and angiogenesis. We aim to understand the mechanisms of skeletal stem cell recruitment from bone marrow and periosteum, the tissue that lies at the outer surface of bone, and that we showed is the major contributor to skeletal repair. We study the ontogeny of skeletal stem cells, how they are established during the development and growth of the skeleton in genetic mouse models and how they are affected in genetic diseases.

2- Role of muscle-bone interactions in musculoskeletal regeneration

The recruitment of skeletal stem cells in bone defects or injuries occurs in an inflammatory environment and is influenced by environmental mechanical signals and the surrounding tissues such as muscle. Bone and skeletal muscle are closely linked across development, growth and aging. Genetic disorders affecting muscle such as Duchenne Muscular Dystrophy (DMD) also impact bone and we have shown that bone regeneration is deficient in a mouse model of DMD. Similarly, loss of bone quality in osteoporosis is linked with sarcopenia. While it is generally recognized that muscle plays an important role in bone healing, the mechanisms of action remain poorly understood. In this project, we investigate the cellular and molecular contributions of muscle to bone repair, by identifying muscle-derived stem cells and growth factors involved in bone repair, and by assessing the impact of muscle injury on skeletal stem cell activation within periosteum.