Dataset Information

The role of muscle loading on bone (Re)modeling at the developing enthesis.

ABSTRACT: Muscle forces are necessary for the development and maintenance of a mineralized skeleton. Removal of loads leads to malformed bones and impaired musculoskeletal function due to changes in bone (re)modeling. In the current study, the development of a mineralized junction at the interface between muscle and bone was examined under normal and impaired loading conditions. Unilateral mouse rotator cuff muscles were paralyzed using botulinum toxin A at birth. Control groups consisted of contralateral shoulders injected with saline and a separate group of normal mice. It was hypothesized that muscle unloading would suppress bone formation and enhance bone resorption at the enthesis, and that the unloading-induced bony defects could be rescued by suppressing osteoclast activity. In order to modulate osteoclast activity, mice were injected with the bisphosphonate alendronate. Bone formation was measured at the tendon enthesis using alizarin and calcein fluorescent labeling of bone surfaces followed by quantitative histomorphometry of histologic sections. Bone volume and architecture was measured using micro computed tomography. Osteoclast surface was determined via quantitative histomorphometry of tartrate resistant acid phosphatase stained histologic sections. Muscle unloading resulted in delayed initiation of endochondral ossification at the enthesis, but did not impair bone formation rate. Unloading led to severe defects in bone volume and trabecular bone architecture. These defects were partially rescued by suppression of osteoclast activity through alendronate treatment, and the effect of alendronate was dose dependent. Similarly, bone formation rate was increased with increasing alendronate dose across loading groups. The bony defects caused by unloading were therefore likely due to maintained high osteoclast activity, which normally decreases from neonatal through mature timepoints. These results have important implications for the treatment of muscle unloading conditions such as neonatal brachial plexus palsy, which results in shoulder paralysis at birth and subsequent defects in the rotator cuff enthesis and humeral head.

SUBMITTER: Tatara AM

PROVIDER: S-EPMC4029607 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The role of muscle loading on bone (Re)modeling at the developing enthesis.

Tatara Alexander M AM Lipner Justin H JH Das Rosalina R Kim H Mike HM Patel Nikunj N Ntouvali Eleni E Silva Matthew J MJ Thomopoulos Stavros S

PloS one 20140521 5

Muscle forces are necessary for the development and maintenance of a mineralized skeleton. Removal of loads leads to malformed bones and impaired musculoskeletal function due to changes in bone (re)modeling. In the current study, the development of a mineralized junction at the interface between muscle and bone was examined under normal and impaired loading conditions. Unilateral mouse rotator cuff muscles were paralyzed using botulinum toxin A at birth. Control groups consisted of contralateral ...[more]

PMID: 24847982

Similar Datasets

Project description:The meniscus acts as a stabilizer, lubricator, and load distributer in the knee joint. The mechanical stability of the meniscus depends on its connection to the underlying bone by a fibrocartilage to bone transition zone called the meniscal enthesis. Tissue engineered menisci hold great promise as a treatment alternative however lack a means of integrated fixation to the underlying bone needed in order for a tissue engineered meniscal replacement to be successful. Tissue engineering the meniscal enthesis is a difficult task given the complex gradients of cell type, mineral, and extracellular matrix molecules. Therefore, there is a need for a simplified and high throughput enthesis model to test experimental parameters. The goal of this study was to develop a simplified enthesis model to test collagen integration with decellularized bone. We found that injection molding collagen into tubing loaded with decellularized bone plugs resulted in a scaffold with three regions: bone, bone-collagen, and collagen. Furthermore, collagen formation was directed in the axial direction by using mechanical fixation at the bony ends. The results of this study showed that this technique can be used to mimic the native enthesis morphology and serves as ideal test platform to generate a model tissue engineered enthesis. STATEMENT OF SIGNIFICANCE:The meniscal enthesis is a complex structure that is essential to mechanical stability of the meniscus and the knee joint. Several studies document the development of anatomically shaped tissue engineered meniscus constructs, but none have focused on how to integrate such tissues with underlying bone. This study establishes a simplified construct to model the meniscal enthesis composed of a collagen gel seeded with meniscal fibrochondrocytes integrated with decellularized cancellous bone. Mechanical fixation at the bony ends induced tissue integration of fibers into the bony tissue, which is critical for mechanical performance and has yet to be shown in enthesis literature. Our test platform is amenable to targeted experiments investigating mineralization gradients, collagen fiber alignment, cell population phenotype, and media conditioning with experimental impact on enthesis studies for meniscus, tendon, and ligament.

Dataset Information

The role of muscle loading on bone (Re)modeling at the developing enthesis.

Publications

The role of muscle loading on bone (Re)modeling at the developing enthesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets