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Prenatal murine skeletogenesis partially recovers from absent skeletal muscle as development progresses

DOI: 10.22203/eCM.v044a08 DOI Help

Authors: V. Sotiriou (Imperial College London) , Y. Huang (Imperial College London) , S. Ahmed (Imperial College London) , H. Isaksson (Lund University) , N, C. Nowlan (Imperial College London; University College Dublin)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: European Cells And Materials , VOL 44 , PAGES 115 - 132

State: Published (Approved)
Published: November 2022
Diamond Proposal Number(s): 16557

Open Access Open Access

Abstract: Skeletal muscle contractions are critical for normal skeletal growth and morphogenesis but it is unclear how the detrimental effects of absent muscle on the bones and joints change over time. Joint shape and cavitation as well as rudiment length and mineralisation were assessed in multiple rudiments at two developmental stages [Theiler stage (TS)24 and TS27] in the splotch-delayed “muscle-less limb” mouse model and littermate controls. Chondrocyte morphology was quantified in 3D in the distal humerus at the same stages. As development progressed, the effects of absent muscle on all parameters except for cavitation become less severe. All major joints in muscle-less limbs were abnormally shaped at TS24, while, by TS27, most muscle-less limb joint shapes were normal or nearly normal. In contrast, any joints that were fused at TS24 did not cavitate by TS27. At TS24, chondrocytes in the distal humerus were significantly smaller in the muscle-less limbs than in controls, while by TS27, chondrocyte volume was similar between the two groups, offering a cell-level mechanism for the partial recovery in shape of muscle-less limbs. Mineralisation showed the most pronounced changes over gestation. At TS24, all muscle-less rudiments studied had less mineralisation than the controls, while at TS27, muscle-less limb rudiments had mineralisation extents equivalent to controls. In conclusion, the effects of muscle absence on prenatal murine skeletogenesis reduced in severity over gestation. Understanding how mammalian bones and joints continue to develop in an environment with abnormal fetal movements provides insights into conditions including hip dysplasia and arthrogryposis.

Journal Keywords: Prenatal skeletal development; fetal movements; developmental biomechanics; cartilage; bone; morphogenesis; ossification; mouse

Diamond Keywords: Bone

Subject Areas: Biology and Bio-materials

Instruments: I13-2-Diamond Manchester Imaging

Added On: 08/11/2022 14:34


Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Life Sciences & Biotech

Technical Tags:

Imaging Tomography