# Morphogenetic development of trochlear groove and thigh muscles from embryo to fetus in humans

**Authors:** Aoi Ishikawa, Momoko Nagai-Tanima, Kanon Ishida, Hirohiko Imai, Akio Yoneyama, Shigehito Yamada, Hiroki Otani, Tomoki Aoyama, Tetsuya Takakuwa

PMC · DOI: 10.1371/journal.pone.0339167 · PLOS One · 2026-02-02

## TL;DR

This study investigates how the knee joint and thigh muscles develop from embryos to fetuses, showing how fetal movements influence musculoskeletal growth.

## Contribution

The study provides new insights into the synchronized development of knee joint morphology and fetal movement from an embryonic to fetal stage.

## Key findings

- The trochlear groove angle decreases until 120 mm CRL and stabilizes until 185 mm CRL.
- Fetal joint motion increases slowly until 100 mm CRL and then rapidly.
- Stabilization of joint morphology coincides with increased muscle mass and joint motion.

## Abstract

Mechanical forces caused by fetal movements are essential for normal musculoskeletal development. However, the relationship between skeletal development and knee joint motion in utero remains unclear. We aimed to clarify the development of lower limb musculoskeletal structures during the embryonic and early fetal stages from a kinematic perspective and to compare muscle and skeletal developmental processes. We analyzed 29 human embryonic and fetal specimens. Using phase-contrast X-ray computed tomography and magnetic resonance imaging, we analyzed the morphogenesis of the knee joint components, trochlear groove angle, and hypothetical joint motion of the thigh muscles in three dimensions. To analyze chronological morphogenesis, Procrustes analysis was performed, and Principal component analysis and linear discriminant analysis were subsequently conducted using the Procrustes coordinates. The trochlear groove angle on the plane vertical to the femoral axis decreased from approximately 160° to 130° until 120 mm Crown-rump length (CRL) and remained constant until 185 mm CRL. All hypothetical joint motions increased slowly between 30 and 100 mm CRL, whereas rapidly after approximately 100 mm CRL. The protrusions of the lateral femoral condyle became more pronounced from fetal stage as they grew. The timing of the onset of fetal movement and the increase in muscle mass and joint motion during early pregnancy were consistent with those of previous studies, and the timing of the angle stabilization occurred almost simultaneously with the rapid increase in femoral muscle mass and hypothesized joint motion. It suggested that stabilization of joint morphology enables smooth joint motion, which leads to an increase in muscle mass and joint motion.

## Linked entities

- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** WNT9A (Wnt family member 9A) [NCBI Gene 7483] {aka WNT14}, BMP4 (bone morphogenetic protein 4) [NCBI Gene 652] {aka BMP2B, BMP2B1, MCOPS6, OFC11, ZYME}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, SOX9 (SRY-box transcription factor 9) [NCBI Gene 6662] {aka CMD1, CMPD1, ENH13, SRA1, SRXX2, SRXY10}, IL31RA (interleukin 31 receptor A) [NCBI Gene 133396] {aka CRL, CRL3, GLM-R, GLMR, GPL, IL-31RA}, PCSK1 (proprotein convertase subtilisin/kexin type 1) [NCBI Gene 5122] {aka BMIQ12, NEC1, PC1, PC1/3, PC3, SPC3}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, SCX (scleraxis bHLH transcription factor) [NCBI Gene 642658] {aka SCXA, SCXB, bHLHa48}
- **Diseases:** hip dysplasia (MESH:D006617), muscle dysgenesis (MESH:C537048), muscle loss (MESH:D009135), GA (MESH:C536833), Trochlear dysplasia (MESH:D020432), patellofemoral instability (MESH:D046788), patellar dislocation (MESH:D031222), dysplasia of the trochlear groove (MESH:D000652), pain (MESH:D010146), arthritis (MESH:D001168), Congenital Anomaly (MESH:D000013)
- **Chemicals:** agarose (MESH:D012685), GA (MESH:D005708), formalin (MESH:D005557), LA (-), eosin (MESH:D004801), Si (MESH:D012825), water (MESH:D014867), hematoxylin (MESH:D006416)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12863510/full.md

## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12863510/full.md

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Source: https://tomesphere.com/paper/PMC12863510