Perilacunar bone tissue exhibits sub-micrometer modulus gradation which depends on the recency of osteocyte bone formation in both young adult and early-old-age female C57Bl/6 mice

Rux, Caleb J.; Vahidi, Ghazal; Darabi, Amir; Cox, Lewis M.; Heveran, Chelsea M.

doi:10.1016/j.bone.2022.116327

Cited by 15 publications

(11 citation statements)

References 68 publications

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“…Previous studies show that the release in compressive load indicates ACL rupture, as verified by later dissection 7,8 . Another limitation is that embedding bone in PMMA significantly stiffens bone tissue compared with the hydrated condition 33,50 . However, preparing the subchondral bone plate for microscale modulus measurement required stabilizing this small structure with an infiltrating embedding material.…”

Section: Discussionmentioning

confidence: 99%

Subchondral bone and synovial fluid metabolomic profiles are altered in injured and contralateral limbs 7 days after non-invasive joint injury in skeletally-mature C57BL/6 mice

Hislop¹,

Devine

June

et al. 2022

Preprint

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Objective: Post-traumatic osteoarthritis (PTOA) is a common long-term outcome following ACL injury. However, early changes to bone and synovial fluid after ACL injury are not sufficiently understood. The objectives of this study were to (1) evaluate whether acute bone loss one week after ACL injury is accompanied by altered subchondral bone plate modulus, (2) determine if bone changes are localized to the injured limb or extend to the contralateral-to-injured limb compared with sham-loaded controls, and (3) identify shifts in synovial fluid metabolism unique to injured limbs. Design: Female C57Bl\6N mice (19 weeks at injury) were subjected to either a single tibial compression overload to simulate ACL injury (n=8) or a small pre-load (n=8). Mice were euthanized 7 days after injury, and synovial fluid was immediately harvested for metabolomic profiling. Bone microarchitecture, bone formation, and subchondral bone modulus at the proximal tibia were studied using microCT, histomorphometry, and nanoindentation, respectively. Osteoclast number density was assessed at the distal femur. For each bone measure a mixed model ANOVA was generated to determine the effects of injury and loaded side. Results: Epiphyseal and subchondral bone microarchitecture decreased while subchondral bone tissue modulus was unchanged after ACL injuries. Bone resorption increased but bone formation was not changed. Loss of bone microarchitecture also occurred for the contralateral-to-injured limb, demonstrating that the early response to ACL injury extended beyond the injured joint. While the metabolomic profiles of the injured and contralateral-to-injured limbs had many similarities, there were also distinct metabolic shifts present in only the injured limbs. The most prominent of the pathways was cysteine and methionine metabolism, which is associated with osteoclast activity. Conclusion: These results add to the understanding of early bone changes following ACL injury. Confirming prior reports, we observe a decline in epiphyseal and subchondral bone microarchitecture. We add the finding that subchondral bone modulus remains unchanged at one week after ACL injury. A potential biomarker of this initial bone catabolic response may be synovial fluid cysteine and methionine metabolism, which was only dysregulated in injured knees. Our results implicate a rapidly changing biological and mechanical environment within both the injured and contralateral joints that has the potential for influencing the progression to PTOA.

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Section: Discussionmentioning

confidence: 99%

Subchondral bone and synovial fluid metabolomic profiles are altered in injured and contralateral limbs 7 days after non-invasive joint injury in skeletally-mature C57BL/6 mice

Hislop¹,

Devine

June

et al. 2022

Preprint

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“…As an example, it has recently been measured that there is a decrease in elastic modulus with an increasing distance to the lacunar wall. Interestingly, the gradient magnitude is believed to be associated with the age of the osteocyte trapped within the studied lacuna (Rux et al, 2022). Similarly, if the PCM is mainly composed of perlecan, other components could influence the fluid behavior within the LCN (Wang, 2018).…”

Section: How Does the Osteocyte Sense A Mechanical Signal?mentioning

confidence: 96%

“…Although bone is a complex material that presents heterogeneity at all length scales associated with mechanical properties (Bala et al, 2012;Rho et al, 1998;Rux et al, 2022), the following investigation will focus only on the bone porous network. At the macroscale, two bone tissues can be distinguished in terms of their porosities: trabecular bone being porous, and cortical bone being compact ( (Nawathe et al, 2015), Fig.…”

Section: What Is Bone Mechanical Integrity?mentioning

confidence: 99%

Osteocyte pericellular and perilacunar matrices as markers of bone–implant mechanical integrity

Gauthier¹,

Follet²,

Trunfio-Sfarghiu³

et al. 2022

Biocell

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To develop durable bone healing strategies through improved control of bone repair, it is of critical importance to understand the mechanisms of bone mechanical integrity when in contact with biomaterials and implants. Bone mechanical integrity is defined here as the adaptation of structural properties of remodeled bone in regard to an applied mechanical loading. Accordingly, the authors present why future investigations in bone repair and regeneration should emphasize on the matrix surrounding the osteocytes. Osteocytes are mechanosensitive cells considered as the orchestrators of bone remodeling, which is the biological process involved in bone homeostasis. These bone cells are trapped in an interconnected porous network, the lacunocanalicular network, which is embedded in a bone mineralized extracellular matrix. As a consequence of an applied mechanical loading, the bone deformation results in the deformation of this lacunocanalicular network inducing a shift in interstitial fluid pressure and velocity, thus resulting in osteocyte stimulation.The material environment surrounding each osteocyte, the so called perilacunar and pericellular matrices properties, define its mechanosensitivity. While this mechanical stimulation pathway is well known, the laws used to predict bone remodeling are based on strains developing at a tissue scale, suggesting that these strains are related to the shift in fluid pressure and velocity at the lacunocanalicular scale. While this relationship has been validated through observation in healthy bone, the fluid behavior at the bone-implant interface is more complex. The presence of the implant modifies fluid behavior, so that for the same strain at a tissue scale, the shift in fluid pressure and velocity will be different than in a healthy bone tissue. In that context, new markers for bone mechanical integrity, considering fluid behavior, have to be defined. The viewpoint exposed by the authors indicates that the properties of the pericellular and the perilacunar matrices have to be systematically investigated and used as structural markers of fluid behavior in the course of bone biomaterial development.

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“…When mice are injected with fluorochrome labels after weaning, abundant fluorochrome labels are observed 24,32 . However, labeled osteocyte lacunae are also seen in a number of studies where rodents were not under applied calcium pressure 30,32,34,35 , which suggests that osteocyte LCS mineralization may be a more widespread phenomena than has been previously appreciated. For example, we previously demonstrated that ∼60% of randomly-selected lacunae from the femoral midshaft cross-section were labeled with calcein administered 2 days before euthanasia in 5-month and 22-month female C57BL/6 mice 34 .…”

Section: Introductionmentioning

confidence: 92%

Aging decreases osteocyte lacunar-canalicular turnover in female C57BL/6 mice

Vahidi,

Boone,

Hoffman

et al. 2023

Preprint

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Osteocytes engage in bone resorption and mineralization surrounding their expansive lacunar-canalicular system (LCS) through LCS turnover. However, fundamental questions persist about where, when, and how often osteocytes engage in LCS turnover and how these processes change with aging. Furthermore, whether LCS turnover depends on tissue strain remains unexplored. To address these questions, we utilized confocal scanning microscopy, immunohistochemistry, and scanning electron microscopy to characterize osteocyte LCS turnover in the cortical (mid-diaphysis) and cancellous (metaphysis) femurs from young (5 mo) and early-old-age (22 mo) female C57BL/6JN mice. LCS bone mineralization was measured by the presence of perilacunar fluorochrome labels. LCS bone resorption was measured by immunohistochemical markers of bone resorption. The dynamics of LCS turnover were estimated from serial fluorochrome labeling, where each mouse was administered two labels between 2 days and 16 days before euthanasia. Osteocyte participation in mineralizing their surroundings is highly abundant in both cortical and cancellous bone of young adult mice but significantly decreases with aging. LCS bone resorption also decreases with aging. Aging has a greater impact on LCS turnover dynamics in cancellous bone than in cortical bone. Lacunae with recent LCS turnover have larger lacunae in both age groups. The impacts of aging on LCS turnover also varies with cortical region of interest and intracortical location, suggesting a dependence on tissue strain. The impact of aging on decreasing LCS turnover may have significant implications for bone quality and mechanosensation.

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Perilacunar bone tissue exhibits sub-micrometer modulus gradation which depends on the recency of osteocyte bone formation in both young adult and early-old-age female C57Bl/6 mice

Cited by 15 publications

References 68 publications

Subchondral bone and synovial fluid metabolomic profiles are altered in injured and contralateral limbs 7 days after non-invasive joint injury in skeletally-mature C57BL/6 mice

Subchondral bone and synovial fluid metabolomic profiles are altered in injured and contralateral limbs 7 days after non-invasive joint injury in skeletally-mature C57BL/6 mice

Osteocyte pericellular and perilacunar matrices as markers of bone–implant mechanical integrity

Aging decreases osteocyte lacunar-canalicular turnover in female C57BL/6 mice

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