Sixteen weeks of high-speed treadmill running is insufficient to induce Achilles tendinopathy in a rat model.

Despite the high prevalence of Achilles tendinopathy, clinically relevant animal models of Achilles tendinopathy are lacking. Previous studies have demonstrated possible tendinopathic cell and matrix changes with high-speed treadmill running, but the consistency as well as functional and mechanical consequences of these changes were unclear. We sought to determine the applicability of this protocol as a tendinopathy model by defining changes in Achilles tendon structure, function, and mechanics associated with 16 wk of high-speed treadmill running (26.

Moderate- and High-Speed Treadmill Running Exercise Have Minimal Impact on Rat Achilles Tendon.

Exercise influences clinical Achilles tendon health in humans, but animal models of exercise-related Achilles tendon changes are lacking. Moreover, previous investigations of the effects of treadmill running exercise on rat Achilles tendon demonstrate variable outcomes. Our objective was to assess the functional, structural, cellular, and biomechanical impacts of treadmill running exercise on rat Achilles tendon with sensitive in and ex vivo approaches.

Tendon-targeted knockout of collagen XI disrupts patellar and Achilles tendon structure and mechanical properties during murine postnatal development.

Background: Collagen XI is a fibril-forming collagen typically associated with type II collagen tissues but is also expressed in type I collagen-rich tendons, especially during development. We previously showed that tendon-targeted (Scx-Cre) Col11a1 knockout mice have smaller tendons in adulthood with aberrant fibril structure and impaired mechanical properties. However, the manifestation of this phenotype is not clearly understood.

Collagen V haploinsufficiency in female murine patellar tendons results in altered matrix engagement and cellular density, demonstrating decreased healing.

Collagen V (Col5) is a quantitatively minor component of collagen fibrils comprising tendon, however, plays a crucial role in regulation of development and dynamic healing processes. Clinically, patients with COL5a1 haploinsufficiency, known as classic Ehlers-Danlos Syndrome (cEDS), present with hyperextensible skin, joint instability and laxity, with females more likely to be affected. Previous studies in Col5-deficient mice indicated that reduced Col5a1 expression leads to a reduction in stiffness, fibril deposition, and altered fibril structure.

Long-Term Effects of Reproduction and Lactation on the Rat Supraspinatus Tendon and Proximal Humerus.

During pregnancy and breastfeeding, women undergo hormonal fluctuations required for fetal development, parturition, and infant growth. These changes have secondary consequences on the maternal musculoskeletal system, increasing the risk for joint pain and osteoporosis. Though hormone levels return to prepregnancy levels postpartum, women may experience lasting musculoskeletal pain.

Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how).

Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5 to 7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior cruciate ligament tear, and Achilles tendon injury using the framework: "Why, Who, What, Where, When, and How" (5W1H).

Dose-dependent effects of enzyme replacement therapy on skeletal disease progression in mucopolysaccharidosis VII dogs.

Mucopolysaccharidosis (MPS) VII is an inherited lysosomal storage disorder characterized by deficient activity of the enzyme β-glucuronidase. Skeletal abnormalities are common in patients and result in diminished quality of life. Enzyme replacement therapy (ERT) for MPS VII using recombinant human β-glucuronidase (vestronidase alfa) was recently approved for use in patients; however, to date there have been no studies evaluating therapeutic efficacy in a large animal model of MPS VII.

The Non-pregnant and Pregnant Human Cervix: a Systematic Proteomic Analysis.

Appropriate timing of cervical remodeling (CR) is key to normal term parturition. To date, mechanisms behind normal and abnormal (premature or delayed) CR remain unclear. Recent studies show regional differences exist in human cervical tissue structure.

Biglycan has a major role in maintenance of mature tendon mechanics.

Decorin and biglycan are two small leucine-rich proteoglycans (SLRPs) that regulate collagen fibrillogenesis and extracellular matrix assembly in tendon. The objective of this study was to determine the individual roles of these molecules in maintaining the structural and mechanical properties of tendon during homeostasis in mature mice. We hypothesized that knockdown of decorin in mature tendons would result in detrimental changes to tendon structure and mechanics while knockdown of biglycan would have a minor effect on these parameters.

Coordinate roles for collagen VI and biglycan in regulating tendon collagen fibril structure and function.

Tendon is a vital musculoskeletal tissue that is prone to degeneration. Proper tendon maintenance requires complex interactions between extracellular matrix components that remain poorly understood. Collagen VI and biglycan are two matrix molecules that localize pericellularly within tendon and are critical regulators of tissue properties.

Inhibition of glucose use improves structural recovery of injured Achilles tendon in mice.

Injured tendons do not regain their native structure except at fetal or very young ages. Healing tendons often show mucoid degeneration involving accumulation of sulfated glycosaminoglycans (GAGs), but its etiology and molecular base have not been studied substantially. We hypothesized that quality and quantity of gene expression involving the synthesis of proteoglycans having sulfated GAGs are altered in injured tendons and that a reduction in synthesis of sulfated GAGs improves structural and functional recovery of injured tendons.

Evaluation of Autologous Protein Solution Injection for Treatment of Superficial Digital Flexor Tendonitis in an Equine Model.

Autologous protein solution (APS) has been used anecdotally for intralesional treatment of tendon and ligament injuries, however, its use in these injuries has never been studied . Our objective was to evaluate the effect of APS on tendon healing in an equine superficial digital flexor (SDF) tendonitis model. We hypothesized intralesional injection of APS would result in superior structural and biomechanical healing.

Reticulocalbin 3 is involved in postnatal tendon development by regulating collagen fibrillogenesis and cellular maturation.

Tendon plays a critical role in the joint movement by transmitting force from muscle to bone. This transmission of force is facilitated by its specialized structure, which consists of highly aligned extracellular matrix consisting predominantly of type I collagen. Tenocytes, fibroblast-like tendon cells residing between the parallel collagen fibers, regulate this specialized tendon matrix.

MRI-derived porosity index is associated with whole-bone stiffness and mineral density in human cadaveric femora.

Ultrashort echo time (UTE) magnetic resonance imaging (MRI) measures proton signals in cortical bone from two distinct water pools, bound water, or water that is tightly bound to bone matrix, and pore water, or water that is freely moving in the pore spaces in bone. By isolating the signal contribution from the pore water pool, UTE biomarkers can directly quantify cortical bone porosity in vivo. The Porosity Index (PI) is one non-invasive, clinically viable UTE-derived technique that has shown strong associations in the tibia with μCT porosity and other UTE measures of bone water.

Collagen XI regulates the acquisition of collagen fibril structure, organization and functional properties in tendon.

Collagen XI is a fibril-forming collagen that regulates collagen fibrillogenesis. Collagen XI is normally associated with collagen II-containing tissues such as cartilage, but it also is expressed broadly during development in collagen I-containing tissues, including tendons. The goals of this study are to define the roles of collagen XI in regulation of tendon fibrillar structure and the relationship to function.

The Inner Annulus Fibrosus Encroaches on the Nucleus Pulposus in the Injured Mouse Tail Intervertebral Disc.

Objective: The aim was to identify the source of cells within the center of the abnormal fibrocartilage tissue of the degenerative intervertebral disc after injury.

Design: Cross-breeding of mice with an inducible type II promoter collagen construct (Col2CreER) to Rosa26-TdTomato mice has been shown to result in Cre-recombinase activity and Tomato expression in inner annulus fibrosus cells after tamoxifen injection. To investigate the role of the inner annulus fibrosus in the intervertebral disc injury response, tail intervertebral discs of Col2CreER/tdTomato mice were punctured with a needle and examined 1-4 wks after injury.

Induced Knockdown of Decorin, Alone and in Tandem With Biglycan Knockdown, Directly Increases Aged Murine Patellar Tendon Viscoelastic Properties.

Tendon injuries increase with age, yet the age-associated changes in tendon properties remain unexplained. Decorin and biglycan are two matrix proteoglycans that play complex roles in regulating tendon formation, maturation, and aging, most notably in extracellular matrix assembly and maintenance. However, the roles of decorin and biglycan have not been temporally isolated in a homeostatic aged context.

Pregnancy and Lactation Impair Subchondral Bone Leading to Reduced Rat Supraspinatus Tendon-to-Bone Insertion Site Failure Properties.

Pregnant women experience weight gain, gait changes, and biochemical fluctuations that impair joint function and alter the maternal skeleton. Hormonal changes increase pelvic ligament laxity in preparation for childbirth and affect peripheral joint laxity. Calcium demands also rise during pregnancy and lactation, resulting in reduced bone mineral density (BMD) and maternal bone loss.

Short- and Long-Term Exercise Results in a Differential Achilles Tendon Mechanical Response.

The study was conducted to define the biomechanical response of rat Achilles tendon after a single bout of exercise and a short or long duration of daily exercise. We hypothesized that a single bout or a short duration of exercise would cause a transient decrease in Achilles tendon mechanical properties and a long duration of daily exercise would improve these properties. One hundred and thirty-six Sprague-Dawley rats were divided into cage activity (CA) or exercise (EX) groups for a single bout, short-term, or long-term exercise.

MRI-based assessment of proximal femur strength compared to mechanical testing.

Half of the women who sustain a hip fracture would not qualify for osteoporosis treatment based on current DXA-estimated bone mineral density criteria. Therefore, a better approach is needed to determine if an individual is at risk of hip fracture from a fall. The objective of this study was to determine the association between radiation-free MRI-derived bone strength and strain simulations compared to results from direct mechanical testing of cadaveric femora.

MRI-derived bone porosity index correlates to bone composition and mechanical stiffness.

The MRI-derived porosity index (PI) is a non-invasively obtained biomarker based on an ultrashort echo time sequence that images both bound and pore water protons in bone, corresponding to water bound to organic collagenous matrix and freely moving water, respectively. This measure is known to strongly correlate with the actual volumetric cortical bone porosity. However, it is unknown whether PI may also be able to directly quantify bone organic composition and/or mechanical properties.

Amplifying Bone Marrow Progenitors Expressing α-Smooth Muscle Actin Produce Zonal Insertion Sites During Tendon-to-Bone Repair.

Traditional tendon-to-bone repair where the tendon is reattached to bone via suture anchors often results in disorganized scar production rather than the formation of a zonal insertion. In contrast, ligament reconstructions where tendon grafts are passed through bone tunnels can yield zonal tendon-to-bone attachments between the graft and adjacent bone. Therefore, ligament reconstructions can be used to study mechanisms that regulate zonal tendon-to-bone repair in the adult.

Fracture Limits of Maxillary Fourth Premolar Teeth in Domestic Dogs Under Applied Forces.

A cadaveric study was performed to investigate the external mechanical forces required to fracture maxillary fourth premolar teeth in domestic dogs and describe a clinically relevant model of chewing forces placed on functionally important teeth in which fracture patterns are consistent with those defined by the American Veterinary Dental College (AVDC). Twenty-four maxillary fourth premolar teeth were harvested from dog cadavers. Samples consisted of teeth with surrounding alveolar bone potted in polycarbonate cylinders filled with acrylic.