YAP regulates periosteal expansion in fracture repair.

Bone fracture repair initiates by periosteal expansion. The periosteum is typically quiescent, but upon fracture, periosteal cells proliferate and contribute to bone fracture repair. The expansion of the periosteum is regulated by gene transcription; however, the molecular mechanisms behind periosteal expansion are unclear.

Learning on a Limb: An outreach module to engage high school students in orthopaedics.

Orthopaedic researchers need new strategies for engaging underrepresented minority (URM) students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb (LoaL), an orthopaedic research outreach module to teach URM high school students about orthopaedic research.

Learning on a Limb: An outreach module to engage high school students in orthopaedics.

Orthopaedic researchers need new strategies for engaging diverse students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb, an orthopaedic research outreach module to teach diverse high school students about orthopaedic research.

Adjusting to Your Surroundings: An Inquiry-Based Learning Module to Teach Principles of Mechanobiology for Regenerative Medicine.

Mechanobiology is an interdisciplinary field that aims to understand how physical forces impact biological systems. Enhancing our knowledge of mechanobiology has become increasingly important for understanding human disease and developing novel therapeutics. There is a societal need to teach diverse students principles of mechanobiology so that we may collectively expand our knowledge of this subject and apply new principles to improving human health.

YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulation in murine bone development.

Fetal bone development occurs through the conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown.

Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz.

Cells integrate mechanical cues to direct fate specification to maintain tissue function and homeostasis. While disruption of these cues is known to lead to aberrant cell behavior and chronic diseases, such as tendinopathies, the underlying mechanisms by which mechanical signals maintain cell function are not well understood. Here, we show using a model of tendon de-tensioning that loss of tensile cues in vivo acutely changes nuclear morphology, positioning, and expression of catabolic gene programs, resulting in subsequent weakening of the tendon.

YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulated bone development.

Endochondral ossification requires coordinated mobilization of osteoblast precursors with blood vessels. During adult bone homeostasis, vessel adjacent osteoblast precursors respond to and are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Previously, we found that deletion of the mechanoresponsive transcriptional regulators, YAP and TAZ, from Osterix-expressing osteoblast precursors and their progeny caused perinatal lethality.

YAP and TAZ Promote Periosteal Osteoblast Precursor Expansion and Differentiation for Fracture Repair.

In response to bone fracture, periosteal progenitor cells proliferate, expand, and differentiate to form cartilage and bone in the fracture callus. These cellular functions require the coordinated activation of multiple transcriptional programs, and the transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) regulate osteochondroprogenitor activation during endochondral bone development. However, recent observations raise important distinctions between the signaling mechanisms used to control bone morphogenesis and repair.

Gone Caving: Roles of the Transcriptional Regulators YAP and TAZ in Skeletal Development.

Purpose Of Review: The development of the skeleton is controlled by cellular decisions determined by the coordinated activation of multiple transcription factors. Recent evidence suggests that the transcriptional regulator proteins, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), could have important roles in directing the activity of these transcriptional programs. However, in vitro evidence for the roles of YAP and TAZ in skeletal cells has been hopelessly contradictory.

Bioglass incorporation improves mechanical properties and enhances cell-mediated mineralization on electrochemically aligned collagen threads.

Bone tissue engineering mandates the development of a functional scaffold that mimics the physicochemical properties of native bone. Bioglass 45S5 (BG) is a highly bioactive material known to augment bone formation and restoration. Hybrid scaffolds fabricated using collagen type I and BG resemble the organic and inorganic composition of the bone extracellular matrix and hence have been extensively investigated for bone tissue engineering applications.