Structural and Functional Maturation of Distal Femoral Cartilage and Bone During Postnatal Development and Growth in Humans and Mice

Abstract

SYNOPSIS Introduction The size and shape of joints markedly affect their biomechanical properties, but the macroscopic 3-dimensional (3-D) mechanism and extent of cartilage and joint maturation during normal growth are largely unknown. Aims The purposes of this study were to qualitatively illustrate the development of the cartilage-bone interface in the knee during postnatal growth in humans and C57BL/6 wild-type mice, and to quantitatively define the 3-D shape using statistical shape modeling as well as to assess growth strain rates in the mouse distal femur. Methods Clinical computed tomography (CT) scans of asymptomatic knees (0.3–0.6mm in-plane resolution, 0.63mm slice thickness) were obtained from six patients between 4 to 12 years old. Micro-CT scans of mouse knees (9μm isotropic resolution) were from twenty-one mice between 12 to 120 days postnatal. Human and mouse images were compared qualitatively with 2-D images and 3-D reconstructions. Mouse femora shape parameters were determined with statistical shape modeling, and strain rates and directions during growth were mapped. Results The attainment of cartilage-bone interface shape of the distal femur and proximal tibia were qualitatively similar in humans and mice, with marked differences in growth plate morphology. Mouse distal femur shape was described by 11 independent parameters that accounted for >90% of total shape variation during growth. Each shape parameter described changes in specific anatomical regions of the distal femur and varied with age. Shape parameters and strains in the medial and lateral condyles, as well as intercondylar notch, varied greatly between postnatal days 16 to 30. Directions of growth strain across ages corresponded well with the appearance of anatomical landmarks within the distal femur. Conclusion Accurate quantification of the cartilage-bone interface geometry is imperative for furthering the understanding of the macroscopic mechanisms of cartilage maturation and overall joint development.

TAK1 regulates SOX9 expression in chondrocytes and is essential for postnatal development of the growth plate and articular cartilages

“…In contrast, articular chondrocytes have a relatively stable phenotype and maintain an exquisitely organized matrix that is highly resistant to long-term compression and shear forces (Becerra et al, 2010). Development of the articular cartilage continues throughout adolescence in humans and in mice (Chan et al, 2012). Our studies established that TAK1 has an essential role in the postnatal development of the articular cartilage extracellular matrix.…”

“…Articular cartilage first appears during embryogenesis at sites of joint formation, but continues to develop during the postnatal period of skeletal growth (Chan et al, 2012). This unique tissue is avascular and aneural with a high matrix to cell volume ratio and is divided into distinct zones varying in biochemical composition.…”

Permeability and shear modulus of articular cartilage in growing mice

“…In the C57Bl/6 mouse, skeletal maturity is reached between 8 and 9 weeks of age (Chan et al 2012). Proximal femurs were excised, embedded in Technovit Liquid M08 (Jorgensen Labs, Colorado, US), and stored at −20 • C in phosphate-buffered saline (PBS, pH 7.0) supplemented with a protease inhibitor cocktail (Complete, Boehringer Mannheim) at 0.01 %.…”

“…During growth and aging, compositional and structural changes occur in the articular-epiphyseal cartilage regions which influence the material properties (Chan et al 2012). The matrix of cartilage is composed primarily of collagen type II and proteoglycans.…”

3‐dimensional metrics of proximal femoral shape deformities in Legg–Calvé–Perthes disease and slipped capital femoral epiphysis

“…SSM has traditionally been used to find corresponding landmarks between a set of shapes and parameterize differences in shape via a limited number of modes of variation 25 . This technique has been used to quantify differences between normal and diseased shapes 3,26–29 , as well as characterizing growth deformations of the knee 30 . Previously, the authors conducted a study in which a SSM model was created for asymptomatic, LCPD, and SCFE patients.…”