Decreased muscle loading delays maturation of the tendon enthesis during postnatal development

Physical environment influences the development and maintenance of musculoskeletal tissues. The current study uses an animal model to explore the role of the physical environment on the postnatal development of the supraspinatus tendon enthesis. A supraspinatus intramuscular injection of botulinum toxin A was used to paralyze the left shoulders of mice at birth. The supraspinatus muscles of right shoulders were injected with saline to serve as contralateral controls. The supraspinatus enthesis was examined after 14, 21, 28, and 56 days of postnatal development. Histologic assays were used to examine fibrocartilage morphology and percentage osteoclast surface. Micro‐computed tomography was used to examine muscle geometry and bone architecture. At 14 days there were no differences between groups in fibrocartilage formation, muscle geometry, bone architecture, or osteoclast surface. When comparing groups at 21, 28, and 56 days, muscle volume was decreased, fibrocartilage development was delayed, mineralized bone was decreased, and osteoclast surface was higher at each timepoint in the botulinum group compared to the contralateral saline control group. Our results indicate that the development of the tendon enthesis is sensitive to its mechanical environment. A reduction in muscle loading delayed the development of the tendon‐to‐bone insertion site by impeding the accumulation of mineralized bone. Physical factors did not play a significant role in enthesis maturation in the first 14 days postnatally, implying that biologic factors may drive early postnatal development. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1154–1163, 2007

[1]  R. Sokol,et al.  What factors are associated with neonatal injury following shoulder dystocia? , 2006, Journal of Perinatology.

[2]  S. Bain,et al.  Botox induced muscle paralysis rapidly degrades bone. , 2006, Bone.

[3]  W. Herzog,et al.  Acute botulinum toxin‐induced muscle weakness in the anterior cruciate ligament‐deficient rabbit , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[4]  Mollberg Margareta,et al.  High birthweight and shoulder dystocia: the strongest risk factors for obstetrical brachial plexus palsy in a Swedish population‐based study , 2005 .

[5]  W. Herzog,et al.  Frequency and length-dependent effects of Botulinum toxin-induced muscle weakness. , 2005, Journal of biomechanics.

[6]  P. Carter,et al.  Posterior shoulder dislocation in infants with neonatal brachial plexus palsy. , 2004, The Journal of bone and joint surgery. American volume.

[7]  J. McDonald,et al.  Quantification of tartrate resistant acid phosphatase distribution in mouse tibiae using image analysis , 2003, Biotechnic & histochemistry : official publication of the Biological Stain Commission.

[8]  Felix Eckstein,et al.  Precision and Accuracy of Peripheral Quantitative Computed Tomography (pQCT) in the Mouse Skeleton Compared With Histology and Microcomputed Tomography (μCT) , 2003 .

[9]  G. Cranny,et al.  Congenital brachial palsy: incidence, causes, and outcome in the United Kingdom and Republic of Ireland , 2003, Archives of disease in childhood. Fetal and neonatal edition.

[10]  L. Soslowsky,et al.  Variation of biomechanical, structural, and compositional properties along the tendon to bone insertion site , 2003 .

[11]  R. Birch,et al.  Invited Editorial: Obstetric Brachial Plexus Palsy , 2002 .

[12]  Laila M. Aboul Mahasen,et al.  Developmental Morphological and Histological Studies on Structures of the Human Fetal Shoulder Joint , 2001, Cells Tissues Organs.

[13]  D. E. Ashhurst,et al.  The hip joint: the fibrillar collagens associated with development and ageing in the rabbit , 2001, Journal of anatomy.

[14]  J. Foster,et al.  Pharmacology of botulinum toxin. , 2000, Journal of the American Academy of Dermatology.

[15]  E. Hunziker,et al.  Differential effects of embryonic immobilization on the development of fibrocartilaginous skeletal elements. , 2000, Journal of rehabilitation research and development.

[16]  P. Rüegsegger,et al.  Direct Three‐Dimensional Morphometric Analysis of Human Cancellous Bone: Microstructural Data from Spine, Femur, Iliac Crest, and Calcaneus , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  P. Rüegsegger,et al.  Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography. , 1998, Bone.

[18]  P. Waters,et al.  Glenohumeral Deformity Secondary to Brachial Plexus Birth Palsy , 1998, The Journal of bone and joint surgery. American volume.

[19]  M Oyama,et al.  Identification of types II, IX and X collagens at the insertion site of the bovine achilles tendon. , 1998, Matrix biology : journal of the International Society for Matrix Biology.

[20]  J. Ralphs,et al.  Characterization of collagens and proteoglycans at the insertion of the human Achilles tendon. , 1998, Matrix biology : journal of the International Society for Matrix Biology.

[21]  H. Fujioka,et al.  Changes in the expression of type‐X collagen in the fibrocartilage of rat Achilles tendon attachment during development , 1997, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[22]  D. E. Ashhurst,et al.  Fetal and postnatal development of the patella, patellar tendon and suprapatella in the rabbit; changes in the distribution of the fibrillar collagens , 1997, Journal of anatomy.

[23]  K. Wohlfarth,et al.  Botulinum A toxins: units versus units , 1997, Naunyn-Schmiedeberg's Archives of Pharmacology.

[24]  C. Niyibizi,et al.  Biochemical analysis of collagens at the ligament-bone interface reveals presence of cartilage-specific collagens. , 1996, Archives of biochemistry and biophysics.

[25]  A. Allen,et al.  Perinatal Implications of Shoulder Dystocia , 1995, Obstetrics and gynecology.

[26]  R. Huiskes,et al.  Proposal for the regulatory mechanism of Wolff's law , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[27]  J Kumagai,et al.  Immunohistochemical distribution of type I, II and III collagens in the rabbit supraspinatus tendon insertion. , 1994, Journal of anatomy.

[28]  J. Sandy,et al.  Aggrecan in bovine tendon. , 1994, Matrix biology : journal of the International Society for Matrix Biology.

[29]  I. Sanders,et al.  Quantifying how location and dose of botulinum toxin injections affect muscle paralysis , 1993, Muscle & nerve.

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

[31]  S. Goldstein,et al.  Evaluation of a microcomputed tomography system to study trabecular bone structure , 1990, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[32]  M. Drezner,et al.  Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[33]  S. Woo,et al.  Mechanical properties of tendons and ligaments. II. The relationships of immobilization and exercise on tissue remodeling. , 1982, Biorheology.

[34]  S L Woo,et al.  The effect of immobilization on collagen turnover in connective tissue: a biochemical-biomechanical correlation. , 1982, Acta orthopaedica Scandinavica.

[35]  J. Wolff Das Gesetz der Transformation der Knochen , 1893 .

[36]  Victor Birman,et al.  Collagen fiber orientation at the tendon to bone insertion and its influence on stress concentrations. , 2006, Journal of biomechanics.

[37]  F.C.T. van der Helm,et al.  Analysis of muscle and joint loads , 2005 .

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

[39]  J. Burnell,et al.  Simultaneous demonstration of bone alkaline and acid phosphatase activities in plastic-embedded sections and differential inhibition of the activities , 2004, Histochemistry.

[40]  F. Blevins,et al.  Biology of the rotator cuff tendon. , 1997, The Orthopedic clinics of North America.

[41]  L. Soslowsky,et al.  Biomechanics of the rotator cuff. , 1997, The Orthopedic clinics of North America.

[42]  K. Vogel The effect of compressive loading on proteoglycan turnover in cultured fetal tendon. , 1996, Connective tissue research.

[43]  L. Pearce,et al.  Histologic assessment of dose‐related diffusion and muscle fiber response after therapeutic botulinum a toxin injections , 1994, Movement disorders : official journal of the Movement Disorder Society.

[44]  L. S. Matthews,et al.  Trabecular bone remodeling: an experimental model. , 1991, Journal of biomechanics.

[45]  T. Koob,et al.  Structural specialization in tendons under compression. , 1989, International review of cytology.

[46]  S. Goldstein The mechanical properties of trabecular bone: dependence on anatomic location and function. , 1987, Journal of biomechanics.

[47]  M. Flint,et al.  The effect of tensional load on isolated embryonic chick tendons in organ culture. , 1984, Connective tissue research.