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Golman, M.

Publications and source records attributed to Golman, M..

3 recordsLinked to original sources

Musculoskeletal architecture of the shoulder: A comparative anatomy study in bats and mice informing human rotator cuff function

Overhead motion in humans often leads to shoulder injuries, a consequence of the evolutionary trade-off in glenohumeral joint anatomy that balances stability with mobility. Bats consistently engage in overhead motion during flight, subjecting their shoulders to substantial loading throughout their relatively long lifespan. Remarkably, despite the demands placed on a bats shoulder, instability and rotator cuff tears, which could be fatal to bats in short order, are not observed in nature. We were thus inspired to study functional adaptations in the shoulders of bats that enable this overhead motion. Comparative anatomical studies of the shoulders of bats and mice, similarly-sized quadrupeds, were performed and interpreted using a mathematical model. Scapular anatomy indicated a more prominent role for the infraspinatus muscle in the bat compared to the mouse. Measurements of bat and mice shoulders revealed that the bat glenoid had a larger curvature and arc length than that of mice, providing a larger articulating surface area with and deeper enclosing surface of the humeral head. Modeling results predicted that the bat shoulder is stable over a dramatically larger range of angles compared to the mouse shoulder. These results suggested that adaptations to constraints imposed by the bony anatomy and rotator cuff tendons of the shoulder may contribute to the ability of bats to sustain overhead motion in a high stress, repeated loading environment without injury. Results suggest that bats have evolved unique adaptations in their glenohumeral bony anatomy that reduce stress on the supraspinatus, enhance joint stability, and optimize strength across a broad range of motion.

physiology↗

The role of TGFβ signaling in Gli1+ tendon and enthesis cells

The development of musculoskeletal tissues such as tendon, enthesis, and bone relies on proliferation and differentiation of mesenchymal progenitor cells. Gli1+ cells have been described as putative stem cells in several tissues and are presumed to play critical roles in tissue formation and maintenance. For example, the enthesis, a fibrocartilage tissue that connects tendon to bone, is mineralized postnatally by a pool of Gli1+ progenitor cells. These cells are regulated by hedgehog signaling, but it is unclear if TGF{beta} signaling, necessary for tenogenesis, also plays a role in their behavior. To examine the role of TGF{beta} signaling in Gli1+ cell function, the receptor for TGF{beta}, TbR2, was deleted in Gli1-lineage cells in mice at P5. Decreased TGF{beta} signaling in these cells led to defects in enthesis formation by P56, including deficient bone morphometry underlying the enthesis and decreased mechanical properties. In vitro experiments using Gli1+ cells isolated from mouse tail tendons demonstrated that TGF{beta} controls cell proliferation and differentiation through canonical and non-canonical pathways and that TGF{beta} directly controls the tendon transcription factor scleraxis by binding to its distant enhancer. These results have implications in the development of treatments for tendon and enthesis pathologies.

developmental biology↗

Toughening mechanisms for the attachment of architectured materials: The mechanics of the tendon enthesis

Architectured materials offer tailored mechanical properties but are limited in engineering applications due to challenges in maintaining toughness across their attachments. The enthesis connects tendon and bone, two vastly different architectured materials, and exhibits toughness across a wide range of loadings. Understanding the mechanisms by which this is achieved could inform the development of engineered attachments. Integrating experiments, simulations, and novel imaging that enabled simultaneous observation of mineralized and unmineralized tissues, we identified putative mechanisms of enthesis toughening in a mouse model and then manipulated these mechanisms via in vivo control of mineralization and architecture. Imaging uncovered a fibrous architecture within the enthesis that controls trade-offs between strength and toughness. In vivo models of pathology revealed architectural adaptations that optimize these trade-offs through cross-scale mechanisms including nanoscale protein denaturation, milliscale load-sharing, and macroscale energy absorption. Results suggest strategies for optimizing architecture for tough bimaterial attachments in medicine and engineering. TeaserThe architecture of the tendon-to-bone attachment is designed for toughness.

bioengineering↗