Proline Metabolism

Osteoblasts are secretory cells responsible for producing and secreting the Collagen Type 1 (COL1A1) rich extracellular bone matrix.  Osteoblast differentiation and bone formation are energetically and synthetically demanding due to high rates of protein and matrix biosynthesis.  COL1A1 is comprised of approximately 22% proline which is much higher than most other proteins.  This portends proline may be uniquely required by osteoblasts to maintain both differentiation and bone formation.  Consistent with this, proline consumption and biosynthesis increase during osteoblast differentiation and are regulated by osteogenic signals.  Interestingly, proline oxidation is important for energy production and REDOX homeostasis in different cellular contexts.  However, very little is known about proline in osteoblasts or bone development.  Because of this, we are interested in many aspects of proline metabolism including the following:

  • How is proline uptake regulated during osteoblast differentiation?
  • What are the proline transporters and how are they regulated?
  • How is proline utilized in osteoblasts?
  • What are the molecular signals that regulate proline uptake and metabolism?
  • Does proline oxidation regulate osteoblast energetics?
  • Is proline uptake and metabolism affected with age and in diseases like osteoporosis?
  • Can we stimulate proline uptake and/or metabolism and promote COL1A1 synthesis and bone formation?