Osteocyte mechanosensing following short-term and long-term treatment with sclerostin antibody

Morrell, Andrea E.; Robinson, Samuel T.; Ke, Hua Zhu; Holdsworth, Gill; Guo, Xiaolei

doi:10.1016/j.bone.2021.115967

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…In vivo studies have confirmed that sclerostin monoclonal antibody (Scl-Ab) treatment induced bone formation, mass, and strength ( Yao et al, 2016 ). Scl-Ab products are commercially available including Romosozumab (AMG 785, CDP-785), Blosozumab, and BSP804 ( McClung 2017 ; Morrell et al, 2021 ). These antibody-based treatments are widely used for reducing fracture risk arising from various health conditions, including osteoporosis as well as post-menopause ( Ominsky et al, 2011 ; MacNabb et al, 2016 ).…”

Section: Osteocyte-related Diseases and Treatmentsmentioning

confidence: 99%

The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States

Choi

Kijas

Lauko

et al. 2022

Front. Cell Dev. Biol.

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Bone homeostasis is a dynamic equilibrium between bone-forming osteoblasts and bone-resorbing osteoclasts. This process is primarily controlled by the most abundant and mechanosensitive bone cells, osteocytes, that reside individually, within chambers of porous hydroxyapatite bone matrix. Recent studies have unveiled additional functional roles for osteocytes in directly contributing to local matrix regulation as well as systemic roles through endocrine functions by communicating with distant organs such as the kidney. Osteocyte function is governed largely by both biochemical signaling and the mechanical stimuli exerted on bone. Mechanical stimulation is required to maintain bone health whilst aging and reduced level of loading are known to result in bone loss. To date, both in vivo and in vitro approaches have been established to answer important questions such as the effect of mechanical stimuli, the mechanosensors involved, and the mechanosensitive signaling pathways in osteocytes. However, our understanding of osteocyte mechanotransduction has been limited due to the technical challenges of working with these cells since they are individually embedded within the hard hydroxyapatite bone matrix. This review highlights the current knowledge of the osteocyte functional role in maintaining bone health and the key regulatory pathways of these mechanosensitive cells. Finally, we elaborate on the current therapeutic opportunities offered by existing treatments and the potential for targeting osteocyte-directed signaling.

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Section: Osteocyte-related Diseases and Treatmentsmentioning

confidence: 99%

The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States

Choi

Kijas

Lauko

et al. 2022

Front. Cell Dev. Biol.

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“…Several studies suggested that microporous powders require additional space for bone formation and the cells that penetrate the ceramic matrix prefer pore sizes larger than 100 µm [18]. Other studies suggested that bone formation with microporous powder involvement in ceramic resorption and then followed by deposition of osteoid [19,20].…”

Section: Discussionmentioning

confidence: 99%

Effect of β-TCP Powder Derived from Biomaterials on Regeneration of the Femoral Bone Defects in Rabbits

Atiyah,

Hasan,

Owain

2024

Egyptian Journal of Veterinary Sciences

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he current study evaluated the bone healing process of the β-TCP powder to treat experimentally induced bone defects in rabbit models. The β-TCP powder was prepared using the chemical method, which is characterized by Field Emission Scanning Electron Microscopy (FESEM), and Fourier Transform Infrared Spectroscopy (FTIR) . After that, the β-TCP was converted into powder by applying mechanical compression pressure. Thirty (30) healthy New Zealand male rabbits were divided equally into two groups: the treated group and the control group. The previously prepared β-TCP powder filled the experimentally induced sagittal split fractures at the mid-shaft of the femoral bone in the group treated, while in the control group, the induced bone gaps were left without any treatment. The histopathological results showed normal bone marrow tissue with bone tissue regeneration that extended from both ends of the defect with active osteoblasts toward the powder in the treated group, while in the control group, there was a formation of hyaline cartilage surrounded by trabecular bone along with granulation tissue infiltrated with inflammatory cells, which surrounded the fracture location. The bone marrow examination showed the presence of Megakaryocytes and an increase in erythroid to myeloid in the treated group compared to the control group. The statistical analysis showed a significant increase (P<0.0001) in new bone tissue formation in the treated group as compared with the control group during eight months following surgery. The fibrous tissue formation increased significantly (P<0.0001) in the control group compared to the treated group. Moreover, the current work indicated that the β-TCP powder can be used as a bioactive material for bone tissue regeneration, but it requires more time to be resorbed.

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“…Romosozumab is an FDA-approved antisclerostin antibody therapy indicated for use in the treatment of osteoporosis. Given the well-demonstrated effect of such antibodies on preclinical models, [ 18 ] investigators recently reported on 2 studies using romosozumab to enhance fracture healing in the tibia and the hip. Unfortunately, neither study was able to demonstrate efficacy in clinical practice.…”

Section: Approachesmentioning

confidence: 99%

Enhancing fracture repair: cell-based approaches

Wixted

Challa

Nazarian

2022

OTA International: The Open Access Journal of Orthopaedic Trauma

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Fracture repair is based both on the macrolevel modulation of fracture fragments and the subsequent cellular activity. Surgeons have also long recognized other influences on cellular behavior: the effect of the fracture or subsequent surgery on the available pool of cells present locally in the periosteum, the interrelated effects of fragment displacement, and construct stiffness on healing potential, patient pathophysiology and systemic disease conditions (such as diabetes), and external regulators of the skeletal repair (such as smoking or effect of medications). A wide variety of approaches have been applied to enhancing fracture repair by manipulation of cellular biology. Many of these approaches reflect our growing understanding of the cellular physiology that underlies skeletal regeneration. This review focuses on approaches to manipulating cell lineages, influencing paracrine and autocrine cell signaling, or applying other strategies to influence cell surface receptors and subsequent behavior. Scientists continue to evolve new approaches to pharmacologically enhancing the fracture repair process.

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Osteocyte mechanosensing following short-term and long-term treatment with sclerostin antibody

Cited by 7 publications

References 41 publications

The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States

The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States

Effect of β-TCP Powder Derived from Biomaterials on Regeneration of the Femoral Bone Defects in Rabbits

Enhancing fracture repair: cell-based approaches

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