title: Mechanobiology of TGFβ signaling in the skeleton.
abstract: Physical and biochemical cues play fundamental roles in the skeleton at both the tissue and cellular levels. The precise coordination of these cues is essential for skeletal development and homeostasis, and disruption of this coordination can drive disease progression. The growth factor TGFβ is involved in both the regulation of and cellular response to the physical microenvironment. It is essential to summarize the current findings regarding the mechanisms by which skeletal cells integrate physical and biochemical cues so that we can identify and address remaining gaps that could ultimately improve skeletal health. In this review, we describe the role of TGFβ in mechanobiological signaling in bone and cartilage at the tissue and cellular levels. We provide detail on how static and dynamic physical cues at the macro-level are transmitted to the micro-level, ultimately leading to regulation at each level of the TGFβ pathway and to cell differentiation. The continued integration of engineering and biological approaches is needed to answer many remaining questions, such as the mechanisms by which cells generate a coordinated response to physical and biochemical cues. We propose one such mechanism, through which the combination of TGFβ and an optimal physical microenvironment leads to synergistic induction of downstream TGFβ signaling.
authors.affiliation: University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, CA 94143, United States; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, United States.
authors.forename: Joanna P
authors.initials: JP
authors.lastname: Rys
authors.affiliation: University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, CA 94143, United States; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Monteiro
authors.affiliation: University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, San Francisco, San Francisco, CA 94143, United States; Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, United States; Department of Bioengineering and Therapeutic Sciences, Department of Otolaryngology-Head and Neck Surgery, and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, United States. Electronic address: tamara.alliston@ucsf.edu.
authors.forename: Tamara
authors.initials: T
authors.lastname: Alliston
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D001842:Bone and Bones / Q000502:physiology*; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta