Biomedical subjects

Y F Hsieh

Publications and source records attributed to Y F Hsieh.

At least 19 recordsLinked to original sources

PubMed2001

Mechanical loading of diaphyseal bone in vivo: the strain threshold for an osteogenic response varies with location.

Bone tissue responds to elevated mechanical loading with increased bone formation, which is triggered either directly or indirectly by the mechanical strain engendered in the bone tissue. Previous studies have shown that mechanical strain magnitude must surpass a threshold before bone formation is initiated. The objective of this study was to estimate the strain thresholds at three different locations along the ulna of adult rats. We hypothesized that the strain threshold would be greater in regions of the ulna habitually subjected to larger mechanical strains. New bone formation was measured on the periosteal and endocortical surfaces of the ulnar diaphysis in adult female rats exposed to controlled dynamic loading. Axial, compressive loading was applied daily at five different magnitudes for a period of 2 weeks. Bone formation rate (BFR) was measured, using double-label histomorphometry at the ulnar middiaphysis and at locations 3 mm proximal and 3 mm distal to the middiaphysis. Loading induced lamellar bone formation on the periosteal surface that was greater at the distal ulnar location and lower at the proximal location when compared with the middiaphysis. Likewise, peak strains on the periosteal surface were greatest distally and less proximally. There was a significant dose-response relationship between peak strain magnitude and periosteal new bone formation when the mechanically induced strain surpassed a threshold. The strain threshold varied from 1343 microstrain (mu strain) proximally to 2284 mu strain at the midshaft to 3074 mu strain distally. Unlike the periosteal response to mechanical loading, there was not a clear dose-response relationship between applied load and bone formation on the endocortical surface. Endocortical strains were estimated to be < 20% of periosteal strains and may not have been sufficient to initiate a bone formation response. Our results show that the osteogenic response on the periosteal surface of the ulna depends on peak strain level once a strain threshold is surpassed. The threshold strain is largest distally, where locomotor bone strains are typically higher and smallest proximally where locomotor bone strains are lower.

Animals↗

PubMed2001

Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice.

To test the hypothesis that factors associated with bone strength (i.e., volumetric bone mineral density [vBMD], geometry, and microstructure) have heritable components, we exploited the 12 BXH recombinant inbred (RI) strains of mice derived from C57BL/6J (B6; low bone mass) and C3H/HeJ (C3H; high bone mass) progenitor strains. The femurs and lumbar vertebrae from each BXH RI strain were characterized for phenotypes of vBMD, microstructural, biomechanical, and geometrical properties. Methods included bending (femur) and compression (vertebra) testing, peripheral quantitative computed tomography (pQCT), and microcomputed tomography (microCT). Segregation patterns of femoral and vertebral biomechanical properties among the BXH RI strains suggested polygenic regulation. Femoral biomechanical properties were strongly associated with femoral width in the anteroposterior (AP) direction and cortical thickness--geometric properties with complex genetic regulation. Vertebral vBMD and biomechanical properties measured in BXH RI strains showed a greater variability than either B6 or C3H progenitors, suggesting both progenitor strains have independent subsets of genes that yield similar vBMD and strength. The microCT and pQCT data suggested that the distribution of vertebral mineral into cortical and trabecular compartments is regulated genetically. Although the B6 and C3H progenitors had similar vertebral strength, their vertebral structures were markedly different: B6 had good trabecular bone structure and modest cortical bone mineral content (BMC), whereas C3H had high cortical BMC combined with a deficiency in trabecular structure. These structural traits segregated independently in the BXH RI strains. Finally, vertebral strength was not correlated consistently with femoral strength among the BXH RI strains, suggesting genetic regulation of bone strength is site specific.

Animals↗

PubMed2001

Effects of loading frequency on mechanically induced bone formation.

The anabolic effect of mechanical loading on bone tissue is modulated by loading frequency. The objective of this study was to characterize the new bone formation on the periosteal and endocortical surfaces of the ulnar diaphysis in adult, female rats in response to controlled dynamic loading and to examine the interactions between strain magnitude, loading frequency, and bone formation rate (BFR/BS) for frequencies ranging from 1 to 10 Hz. Cyclic, compressive loading was applied to the ulnas of 60 adult, female rats divided into 12 loading groups. Loading was applied for 360 cycles/day with peak loads ranging from 4.3 to 18N at frequencies of 1, 5, and 10 Hz. After 2 weeks of loading, bone formation on the periosteal and endocortical surfaces of the ulna was quantified using double-label histomorphometry on transverse sections obtained at the middiaphysis. Periosteal bone formation increased in a dose-response manner with peak load at each of the three loading frequencies tested. Loading frequency significantly affected the x intercepts and slopes of the peak strain versus BFR/BS (p < 0.001) and peak strain versus mineralizing surface (MS/BS; p < 0.001) curves. Periosteal osteogenesis was best predicted by a mathematical model that assumed: (1) bone cells are activated by fluid shear stresses and (2) that stiffness of the bone cells and the extracellular matrix near the cells increases at higher loading frequencies because of viscoelasticity. Consequently, mechanotransduction appears to involve a complex interaction between extracellular fluid forces and cellular mechanics.

Animals↗

PubMed2000

The effects of transection and reconstruction of the ulnar collateral ligament complex on the position of the proximal phalanx of the thumb during simulated tip pinch.

Injuries to the ulnar collateral ligament (UCL) of the metacarpophalangeal joint of the thumb are common and may result in functional instability of the joint. Eight cadaveric hands were studied. Physiologic levels of muscle loads were applied to the extrinsic flexor tendon of the thumb to simulate tip pinch of the thumb. We investigated the effects of transection of the UCL and accessory UCL (UCL complex) with and without transection of the dorsal capsule and volar plate and of reconstruction of the UCL, for 2 surgical techniques, on the position of the proximal phalanx with respect to the thumb metacarpal. The spatial positions of the metacarpal and proximal phalanx were measured with a 6 degrees of freedom digitizing system for flexion angles from 0 degrees to 60 degrees in 15 degrees increments. Transection of the UCL complex, dorsal capsule, and volar plate (ulnar capsuloligamentous structures) of the metacarpophalangeal joint did not affect radioulnar deviation or radioulnar shift, but did produce significant increases in supination by 8 degrees and volar translation by 2 mm at 45 degrees and 60 degrees compared with those found for the intact joint. The UCL was reconstructed with a tendon graft using the autogenous extensor digiti quinti. The first surgical technique, a traditional technique, and the second surgical technique, a technique based on anatomy, returned the position of the proximal phalanx on the metacarpal head to normal, with the exceptions of volar translation of the proximal phalanx at 60 degrees and trends toward abnormal supination of the proximal phalanx for flexion angels of 45 degrees and 60 degrees.

Adult↗

PubMed2000

Effects of reconstructed radial collateral ligament on index finger mechanics.

Twenty fresh frozen hand specimens from cadavers were studied. Physiologic levels of extrinsic muscle loads were applied to the extrinsic flexor tendons of the index finger to simulate tip pinch of the finger on a fixed plate. The acute effects of transection of the radial collateral ligament and accessory radial collateral ligament (radial collateral ligament complex) with and without transection of the dorsal capsule and volar plate on the position of the proximal phalanx with respect to the metacarpal bone of the index finger were investigated. The acute effects of reconstruction of the radial collateral ligament, for each of two different surgical techniques, on the position of the proximal phalanx also were investigated. The spatial positions of the metacarpal bone and proximal phalanx were measured with a six-degree-of-freedom digitizing system for flexion angles from 0 degrees to 90 degrees in increments of 15 degrees. Transection of the radial collateral ligament complex resulted in significant increases in ulnar deviation (adduction) of the proximal phalanx and in volar translation. Additional transection of the dorsal capsule and volar plate caused significant increases in ulnar deviation, pronation, volar translation, and ulnar shift. The first surgical technique, one traditionally used to reconstruct the metacarpophalangeal joint of the thumb, failed to return the three-dimensional position of the proximal phalanx on the metacarpal head of the index finger to normal. The second surgical technique, based on anatomy, returned the position of the proximal phalanx to levels not statistically different from normal for most flexion angles.

Adult↗

PubMed2000

Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice.

The inbred strains of mice C57BL/6J (B6) and C3H/HeJ (C3H) have very different femoral peak bone densities and may serve as models for studying the genetic regulation of bone mass. Our objective was to further define the bone biomechanics and microstructure of these two inbred strains. Microarchitecture of the proximal femur, femoral midshaft, and lumbar vertebrae were evaluated in three dimensions using microcomputed tomography (microCT) with an isotropic voxel size of 17 microm. Mineralization of the distal femur was determined using quantitative back-scatter electron (BSE) imaging. MicroCT images suggested that C3H mice had thicker femoral and vertebral cortices compared with B6. The C3H bone tissue also was more highly mineralized. However, C3H mice had few trabeculae in the vertebral bodies, femoral neck, and greater trochanter. The trabecular number (Tb.N) in the C3H vertebral bodies was about half of that in B6 vertebrae (2.8(-1) +/- 0.1 mm(-1) vs. 5.1(-1) +/- 0.2 mm(-1); p < 0.0001). The thick, more highly mineralized femoral cortex of C3H mice resulted in greater bending strength of the femoral diaphysis (62.1 +/- 1.2N vs. 27.4 +/- 0.5N, p < 0.0001). In contrast, strengths of the lumbar vertebra were not significantly different between inbred strains (p = 0.5), presumably because the thicker cortices were combined with inferior trabecular structure in the vertebrae of C3H mice. These results indicate that C3H mice benefit from alleles that enhance femoral strength but paradoxically are deficient in trabecular bone structure in the lumbar vertebrae.

Animals↗

PubMed1999

Viscoelastic response of the rat loading model: implications for studies of strain-adaptive bone formation.

Studies of the adaptive skeletal response to mechanical loading require appropriate animal models. Two new approaches involve the nonsurgical application of loads to either the ulna or tibia of rats. Both of these approaches require the loading of bone through adjacent soft tissues, and thus the tissue viscoelasticity might affect the way load is transferred to the bone. The objective of this study was to characterize the mechanical strain in the rat tibia or ulna during applied loading at different frequencies. For the rat ulna model, loading was applied to the ulnae of four adult, female rats as a haversine waveform at frequencies of 1, 2, 5, 10, and 20 Hz and peak loads of 5, 10, 15, and 20 N. Mechanical strain was measured on the medial and lateral ulnar surfaces using single element strain gauges. For the rat tibia model, four-point bending loads were applied to the right tibiae of seven rats at frequencies of 0.5, 1, 2, 5, 10, and 20 Hz and peak loads of 30, 40, 50, and 60 N. Mechanical strain was measured on the lateral tibial surface at 5 mm proximal to the tibiofibular junction. We found that peak strains were linearly proportional to applied load, but decreased logarithmically as loading frequency was increased, indicating a significant viscoelastic effect in the soft tissues surrounding the ulnocarpal joint and in the soft tissues surrounding the tibia shaft. The viscoelastic response of the ulna and tibia tends to "filter out" high-frequency loading components and, as a result, the rat loading systems act as a low-pass filter. Consequently, any experiment designed to test the effect of loading frequency on bone formation in the rat ulna and tibia should employ progressively larger loads at higher loading frequencies to guarantee a consistent peak strain magnitude in the bone. The filtering effect of the ulna loading system is illustrated by an analysis of the strain waveforms from the recent study by Mosley and Lanyon (Bone 23:313-318; 1998) that was designed to evaluate the effect of strain rate on bone formation.

Adaptation, Physiological↗

PubMed1998

Increasing quadriceps loads affect the lengths of the ligaments and the kinematics of the knee.

The relationships between the lengths of the ligaments and kinematics of the knee and quadriceps load, for low to physiologic levels of quadriceps loads, have not previously been studied. We investigated the effects of increasing levels of quadriceps force, necessary to balance increasing levels of externally applied flexion moments, on the kinematics of the tibiofemoral joint and on the separation distances between insertions of selected fibers of the major ligaments of the knee in twelve cadavera. Static measurements were made using a six-degree-of-freedom digitizer for flexion angles ranging from 0 to 120 deg in 15 deg increments. Quadriceps generated extension of the knee was performed by applying loads to the quadriceps tendon to equilibrate each of four magnitudes of external flexion moments equivalent to 8.33, 16.67, 25.00, and 33.33 percent of values previously reported for maximum isometric extension moments. The magnitude of quadriceps force increased linearly (p < 0.0001) as external flexion moment increased throughout the entire range of flexion. Anterior translation, internal rotation, and abduction of the tibia increased linearly (p < 0.0001, p < 0.001, p < 0.001) as external flexion moment and, hence, quadriceps load increased. For the fibers studied, the anterior cruciate ligament (p < 0.0076), posterior cruciate ligament (p < 0.0001), and medial collateral ligament (p < 0.0383) lengthened linearly while the lateral collateral ligament (p < 0.0124) shortened linearly as quadriceps load increased. Based on these results for low to physiologic levels of quadriceps loads, it is reasonable to assume that the ligament lengths or knee kinematics expected with higher quadriceps loads can be extrapolated.

Adult↗

PubMed1998

Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions.

Mechanical stimulation of bone induces new bone formation in vivo and increases the metabolic activity and gene expression of osteoblasts in culture. We investigated the role of the actin cytoskeleton and actin-membrane interactions in the transmission of mechanical signals leading to altered gene expression in cultured MC3T3-E1 osteoblasts. Application of fluid shear to osteoblasts caused reorganization of actin filaments into contractile stress fibers and involved recruitment of beta1-integrins and alpha-actinin to focal adhesions. Fluid shear also increased expression of two proteins linked to mechanotransduction in vivo, cyclooxygenase-2 (COX-2) and the early response gene product c-fos. Inhibition of actin stress fiber development by treatment of cells with cytochalasin D, by expression of a dominant negative form of the small GTPase Rho, or by microinjection into cells of a proteolytic fragment of alpha-actinin that inhibits alpha-actinin-mediated anchoring of actin filaments to integrins at the plasma membrane each blocked fluid-shear-induced gene expression in osteoblasts. We conclude that fluid shear-induced mechanical signaling in osteoblasts leads to increased expression of COX-2 and c-Fos through a mechanism that involves reorganization of the actin cytoskeleton. Thus Rho-mediated stress fiber formation and the alpha-actinin-dependent anchorage of stress fibers to integrins in focal adhesions may promote fluid shear-induced metabolic changes in bone cells.

Actin Cytoskeleton↗

PubMed1997

Multidimensional chromatography coupled with mass spectrometry for target-based screening.

The synthesis of structural analogs and the process of drug discovery have evolved dramatically through recent advances in solid-phase synthesis reagents and automated screening systems. As molecular diversity strategies emerge, the need for automated target-based selection of lead candidates becomes equally important. Multidimensional automated chromatographic techniques coupled to electrospray ionization mass spectrometry facilitate the selection process and provide maximum characterization information in a single screening run. The capture of tightly bound affinity leads by target biomolecules, followed by subsequent release and high-resolution separation with sensitive detection, significantly reduces the time required to identify and characterize lead compounds. This automated multidimensional chromatographic approach coupled with mass spectrometry, Selectronics, was used with several organic and natural libraries to demonstrate an automated target-based screening technique to select for high-affinity binders as potential lead compounds.

Amino Acid Isomerases↗

PubMed1992

Effects of tibial rotations on patellar tracking and patello-femoral contact areas.

The object of this study is to determine the effect of tibial rotations on the three-dimensional patello-femoral motions and contact areas during a physiological loading condition, the knee-extension exercise. A commercially available device, the 3-SPACE digitizer and tracker system, was used to collect the motion data, utilizing cadaveric human lower limbs as well as the geometric measurements describing the articular surfaces at the patello-femoral joint. It was found that tibial rotations caused statistically significant differences, at the 0.05 level, in patellar tilt, patellar rotation and patellar medial-lateral shift. It was also found that while the magnitude of the total contact area at a given knee flexion angle did not change significantly with tibial rotations, medial and lateral components of the total contact areas were affected by tibial rotations. Medical femoral contact areas increased with internal tibial rotations at all flexion angles; lateral femoral contact areas increased with external tibial rotations at all flexion angles. This correlates well with the kinematic data since it was found that the patella shifted medially with internal tibial rotations at all flexion angles, and titled more medially near full-extension causing an increase in the medial contact areas and a decrease in the lateral contact areas.

Biomechanical Phenomena↗

PubMed1982