Mechanobiology of Embryonic Limb Development

Abstract:  Considerable evidence exists to support the hypothesis that mechanical forces have an essential role in healthy embryonic skeletal development. Clinical observations and experimental data indicate the importance of muscle contractions for limb development. However, the influence of these forces is seldom referred to in biological descriptions of bone development, and perhaps this is due to the fact that the hypothesis that mechanical forces are essential for normal embryonic skeletal development is difficult to test and elaborate experimentally in vivo , particularly in humans. Computational modeling has the potential to address this issue by simulating embryonic growth under a range of loading conditions but the potential of such models has yet to be fully exploited. In this article, we review the literature on mechanobiology of limb development in three main sections: ( a ) experimental alteration of the mechanical environment, ( b ) mechanical properties of embryonic tissues, and ( c ) the use of computational models. Then we analyze the main issues, and suggest how experimental and computational fields could work closer together to enhance our understanding of mechanobiology of the embryonic skeleton.

[1]  A. Pitsillides,et al.  Differential regulation of GDF‐5 and FGF‐2/4 by immobilisation in ovo exposes distinct roles in joint formation , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[2]  J. Mao,et al.  Modulation of endochondral development of the distal femoral condyle by mechanical loading , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[3]  P. Prendergast,et al.  Evolution of mechanoregulation of bone growth will lead to non-optimal bone phenotypes. , 2005, Journal of theoretical biology.

[4]  H. Fritsch,et al.  The role of cartilage canals in endochondral and perichondral bone formation: are there similarities between these two processes? , 2005, Journal of anatomy.

[5]  K. Tanne,et al.  Cyclic Mechanical Strain Regulates the PTHrP Expression in Cultured Chondrocytes via Activation of the Ca2+ Channel , 2005, Journal of dental research.

[6]  R. Huiskes,et al.  The mechanical consequences of mineralization in embryonic bone. , 2004, Bone.

[7]  D. Carter,et al.  Mechanobiological predictions of growth front morphology in developmental hip dysplasia , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[8]  D R Carter,et al.  Mechanical induction in limb morphogenesis: the role of growth-generated strains and pressures. , 2002, Bone.

[9]  A. Pitsillides,et al.  Short-term rigid and flaccid paralyses diminish growth of embryonic chick limbs and abrogate joint cavity formation but differentially preserve pre-cavitated joints. , 2002, Journal of musculoskeletal & neuronal interactions.

[10]  J. Hecksher-Sørensen,et al.  Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies , 2002, Science.

[11]  Rik Huiskes,et al.  Why mechanobiology? A survey article. , 2002, Journal of biomechanics.

[12]  J D Humphrey,et al.  Stress-modulated growth, residual stress, and vascular heterogeneity. , 2001, Journal of biomechanical engineering.

[13]  Albert C. Chen,et al.  Compressive properties and function—composition relationships of developing bovine articular cartilage , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[14]  Yue Zhang,et al.  Indian hedgehog Is an Essential Component of Mechanotransduction Complex to Stimulate Chondrocyte Proliferation* , 2001, The Journal of Biological Chemistry.

[15]  Robert B. Salter,et al.  Skeletal Function and Form. Mechanobiology of Skeletal Development, Aging, and Regeneration. , 2001 .

[16]  D. Carter,et al.  Mechanobiology and joint conformity regulate endochondral ossification of sesamoids , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  L. Blankevoort,et al.  Influence of muscular activity on local mineralization patterns in metatarsals of the embryonic mouse , 2000, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[18]  Borjana Mikic,et al.  Differential effects of embryonic immobilization on the development of fibrocartilaginous skeletal elements. , 2000, Journal of rehabilitation research and development.

[19]  Marjolein C. H. van der Meulen,et al.  Mechanics in skeletal development, adaptation and disease , 2000, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[20]  S. S. Stevens,et al.  Computer model of endochondral growth and ossification in long bones: Biological and mechanobiological influences , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[21]  T. Ochi,et al.  Mechanical Tension‐Stress Induces Expression of Bone Morphogenetic Protein (BMP)‐2 and BMP‐4, but Not BMP‐6, BMP‐7, and GDF‐5 mRNA, During Distraction Osteogenesis , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  J. Heegaard,et al.  Mechanically modulated cartilage growth may regulate joint surface morphogenesis , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  L Blankevoort,et al.  Why does intermittent hydrostatic pressure enhance the mineralization process in fetal cartilage? , 1999, Journal of biomechanics.

[24]  G. Kardon,et al.  Muscle and tendon morphogenesis in the avian hind limb. , 1998, Development.

[25]  Borjana Mikic,et al.  Epigenetic mechanical factors in the evolution of long bone epiphyses , 1998 .

[26]  D. Carter,et al.  Regular ArticleEpigenetic mechanical factors in the evolution of long bone epiphyses , 1998 .

[27]  F. Long,et al.  Regulation of growth region cartilage proliferation and differentiation by perichondrium. , 1998, Development.

[28]  P J Prendergast,et al.  Finite element models in tissue mechanics and orthopaedic implant design. , 1997, Clinical biomechanics.

[29]  S. Goldstein,et al.  Structure and function of embryonic growth plate in the absence of functioning skeletal muscle , 1997, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[30]  G S Beaupré,et al.  Mechanobiologic influences in long bone cross-sectional growth. , 1993, Bone.

[31]  A. Franzén,et al.  Transformation of fetal secondary cartilage into embryonic bone in organ cultures of human mandibular condyles , 1993, Cell and Tissue Research.

[32]  A. Hosseini,et al.  The effects of paralysis on skeletal development in the chick embryo. , 1992, Comparative biochemistry and physiology. Comparative physiology.

[33]  M. Sanchez,et al.  Long bone development in extrinsic fetal akinesia: an experimental study in rat fetuses subjected to oligohydramnios. , 1992, Teratology.

[34]  M. Sanchez,et al.  Morphological changes in long bone development in fetal akinesia deformation sequence: an experimental study in curarized rat fetuses. , 1992, Teratology.

[35]  A. Hosseini,et al.  The effects of paralysis on skeletal development in the chick embryo. I. General effects. , 1991, Journal of anatomy.

[36]  A. Hosseini,et al.  The effects of paralysis on skeletal development in the chick embryo. II. Effects on histogenesis of the tibia. , 1991, Journal of anatomy.

[37]  S W Herring,et al.  Paralysis and growth of the musculoskeletal system in the embryonic chick , 1990, Journal of morphology.

[38]  R. Paniagua,et al.  Effects of immobilization on fetal bone development. A morphometric study in newborns with congenital neuromuscular diseases with intrauterine onset , 1988, Calcified Tissue International.

[39]  D R Carter,et al.  The role of mechanical loading histories in the development of diarthrodial joints , 1988, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[40]  R. Paniagua,et al.  Changes in the long bones due to fetal immobility caused by neuromuscular disease. A radiographic and histological study. , 1988, The Journal of bone and joint surgery. American volume.

[41]  B. Hall,et al.  Earliest evidence of cartilage and bone development in embryonic life. , 1987, Clinical orthopaedics and related research.

[42]  D P Fyhrie,et al.  Influences of Mechanical Stress on Prenatal and Postnatal Skeletal Development , 1987, Clinical orthopaedics and related research.

[43]  E H Burger,et al.  Increased calcification of growth plate cartilage as a result of compressive force in vitro. , 1986, Arthritis and rheumatism.

[44]  E Otten,et al.  Analytical description of growth. , 1982, Journal of theoretical biology.

[45]  H. J. Gamble Histophysiology of Cartilage, Bone and Joints. , 1981 .

[46]  D. Hogg A re-investigation of the centres of ossification in the avian skeleton at and after hatching. , 1980, Journal of anatomy.

[47]  E R Morey,et al.  Inhibition of bone formation during space flight. , 1978, Science.

[48]  L. Landmesser,et al.  The development of functional innervation in the hind limb of the chick embryo. , 1975, The Journal of physiology.

[49]  B. K. Haal Immobilization and cartilage transformation into bone in the embryonic chick , 1972 .

[50]  E. Gardner,et al.  The prenatal development of the human femur. , 1970, The American journal of anatomy.

[51]  P. Murray,et al.  The role of movement in the development of joints and related structures: the head and neck in the chick embryo. , 1969, Journal of embryology and experimental morphology.

[52]  H. B. Fell THE EFFECT OF ENVIRONMENT ON SKELETAL TISSUE IN CULTURE , 1969, Development, growth & differentiation.

[53]  W. E. Koch,et al.  An autoradiographic study of chondrocyte transformation into chondroclasts and osteocytes during bone formation In vitro , 1967, The Anatomical record.

[54]  W. J. Felts Transplantation studies of factors in skeletal organogenesis. I. The subcutaneously implanted immature long-bone of the rat and mouse. , 1959, American journal of physical anthropology.

[55]  G. Lelkes Experiments in vitro on the role of movement in the development of joints. , 1958, Journal of embryology and experimental morphology.

[56]  A. Glucksmann The role of mechanical stresses in bone formation in vitro. , 1942, Journal of anatomy.

[57]  A. Glücksmann Studies on bone mechanics in vitro. II. The role of tension and pressure in chondrogenesis , 1939 .

[58]  R. A. Willis The Growth of Embryo Bones Transplanted Whole in the Rat9s Brain , 1936 .

[59]  H. B. Fell,et al.  Experiments on the Development in vitro of the Avian Knee-Joint , 1934 .

[60]  P. Murray,et al.  Intrinsic and extrinsic factors in the primary development of the skeleton , 1930, Wilhelm Roux' Archiv für Entwicklungsmechanik der Organismen.

[61]  W. Zeit,et al.  Studies in the dynamics of histogenesis. XII. The regeneration of the patellae of dogs , 1927 .

[62]  H. B. Fell The histogenesis of cartilage and bone in the long bones of the embryonic fowl , 1925 .

[63]  Hwj Rik Huiskes,et al.  Geometry of perichondrium determines location of early bone formation in long bones , 2006 .

[64]  Borjana Mikic,et al.  Mechanical Modulation of Cartilage Structure and Function During Embryogenesis in the Chick , 2004, Annals of Biomedical Engineering.

[65]  F. Pauwels,et al.  Eine neue Theorie über den Einfluß mechanischer Reize auf die Differenzierung der Stützgewebe , 2004, Zeitschrift für Anatomie und Entwicklungsgeschichte.

[66]  S. Goldstein,et al.  Neuromuscular atrophy alters collagen gene expression, pattern formation, and mechanical integrity of the chick embryo long bone. , 1993, Progress in clinical and biological research.

[67]  D. Carter,et al.  Theoretical stress analysis of organ culture osteogenesis. , 1990, Bone.

[68]  D P Fyhrie,et al.  Trabecular bone density and loading history: regulation of connective tissue biology by mechanical energy. , 1987, Journal of biomechanics.

[69]  T D Brown,et al.  Experimental determination of the linear biphasic constitutive coefficients of human fetal proximal femoral chondroepiphysis. , 1986, Journal of biomechanics.

[70]  W. Jee,et al.  The Skeletal Tissues , 1983 .

[71]  B. Stokes,et al.  Development of contractile properties in avian embryonic skeletal muscle. , 1982, The American journal of physiology.

[72]  Friedrich Pauwels,et al.  A New Theory Concerning the Influence of Mechanical Stimuli on the Differentiation of the Supporting Tissues , 1980 .

[73]  A. Ham,et al.  Histophysiology of cartilage, bone, and joints , 1979 .

[74]  B. Hall Immobilization and cartilage transformation into bone in the embryonic chick. , 1972, The Anatomical record.

[75]  P. Murray,et al.  Factors in the evocation of adventitious (secondary) cartilage in the chick embryo. , 1965 .

[76]  F. Pauwels,et al.  Eine neue Theorie ber den Einflu mechanischer Reize auf die Differenzierung der Sttzgewebe: Zehnter Beitrag zur funktionellen Anatomie und kausalen Morphologie des Sttzapparates , 1960 .

[77]  H. B. Fell The Osteogenic Capacity in vitro of Periosteum and Endosteum Isolated from the Limb Skeleton of Fowl Embryos and Young Chicks. , 1932, Journal of anatomy.

[78]  H B Fell,et al.  The growth, development and phosphatase activity of embryonic avian femora and limb-buds cultivated in vitro. , 1929, The Biochemical journal.