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Skeletal shape depends on the transmission of contractile muscle forces from tendon to bone across the enthesis. Loss of muscle loading impairs enthesis development, yet little is known if and how the postnatal enthesis adapts to increased loading. Here, we studied adaptations in enthesis structure and function in response to increased loading, using optogenetically induced muscle contraction in young (i.e., growth) and adult (i.e., mature) mice. Daily bouts of unilateral optogenetic loading in young mice led to radial calcaneal expansion and warping. This also led to a weaker enthesis with increased collagen damage in young tendon and enthisis, with little change in adult mice. We then used RNA sequencing to identify the pathways associated with increased mechanical loading during growth. In tendon, we found enrichment of glycolysis, focal adhesion, and cell-matrix interactions. In bone, we found enrichment of inflammation and cell cycle. Together, we demonstrate the utility of optogenetic-induced muscle contraction to elicit in vivo adaptation of the enthesis.
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Deletion of Fibroblast growth factor 9 globally and in skeletal muscle results in enlarged tuberosities at sites of deltoid tendon attachments
Abstract BackgroundThe growth of most bony tuberosities, like the deltoid tuberosity (DT), rely on the transmission of muscle forces at the tendon‐bone attachment during skeletal growth. Tuberosities distribute muscle forces and provide mechanical leverage at attachment sites for joint stability and mobility. The genetic factors that regulate tuberosity growth remain largely unknown. In mouse embryos with global deletion offibroblast growth factor 9(Fgf9), the DT size is notably enlarged. In this study, we explored the tissue‐specific regulation of DT size using both global and targeted deletion ofFgf9. ResultsWe showed that cell hypertrophy and mineralization dynamics of the DT, as well as transcriptional signatures from skeletal muscle but not bone, were influenced by the global loss ofFgf9. Loss ofFgf9during embryonic growth led to increased chondrocyte hypertrophy and reduced cell proliferation at the DT attachment site. This endured hypertrophy and limited proliferation may explain the abnormal mineralization patterns and locally dysregulated expression of markers of endochondral development inFgf9nullattachments. We then showed that targeted deletion ofFgf9in skeletal muscle leads to postnatal enlargement of the DT. ConclusionTaken together, we discovered thatFgf9may play an influential role in muscle‐bone cross‐talk during embryonic and postnatal development.
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- Award ID(s):
- 1944448
- PAR ID:
- 10360641
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Developmental Dynamics
- Volume:
- 250
- Issue:
- 12
- ISSN:
- 1058-8388
- Format(s):
- Medium: X Size: p. 1778-1795
- Size(s):
- p. 1778-1795
- Sponsoring Org:
- National Science Foundation
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