Multiscale bone quality analysis in osteoarthritic knee joints reveal a role of the mechanosensory osteocyte network in osteophytes

Rabelo, Gustavo Davi; Scheidt, Annika vom; Klebig, Felix; Hemmatian, Haniyeh; Citak, Mustafa; Amling, Michael; Busse, Björn; Jähn, Katharina

doi:10.1038/s41598-019-57303-z

Cited by 12 publications

(10 citation statements)

References 59 publications

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“…Osteoid volume per bone volume (OV/BV), the number of osteoblasts/osteoclasts per bone perimeter (N.Ob/B.Pm; N.Oc/B.Pm) and the eroded surface per bone surface (ER/BS) were measured. Osteocyte connectivity was determined as previously established ( 34 ) using Ploton silver–stained sections of the vertebrae, and the number of canaliculi per osteocyte lacuna (N.Ot.Ca/Ot.Lc) was quantified using ImageJ software (ImageJ 1.52, National Institutes of Health, Bethesda, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Compound Heterozygous Frameshift Mutations in MESD Cause a Lethal Syndrome Suggestive of Osteogenesis Imperfecta Type XX

Stürznickel

Jähn‐Rickert

Zustin

et al. 2020

Journal of Bone and Mineral Research

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Multiple genes are known to be associated with osteogenesis imperfecta (OI), a phenotypically and genetically heterogenous bone disorder, marked predominantly by low bone mineral density and increased risk of fractures. Recently, mutations affecting MESD, which encodes for a chaperone required for trafficking of the low‐density lipoprotein receptors LRP5 and LRP6 in the endoplasmic reticulum, were described to cause autosomal‐recessive OI XX in homozygous children. In the present study, whole‐exome sequencing of three stillbirths in one family was performed to evaluate the presence of a hereditary disorder. To further characterize the skeletal phenotype, fetal autopsy, bone histology, and quantitative backscattered electron imaging (qBEI) were performed, and the results were compared with those from an age‐matched control with regular skeletal phenotype. In each of the affected individuals, compound heterozygous mutations in MESD exon 2 and exon 3 were detected. Based on the skeletal phenotype, which was characterized by multiple intrauterine fractures and severe skeletal deformity, OI XX was diagnosed in these individuals. Histological evaluation of MESD specimens revealed an impaired osseous development with an altered osteocyte morphology and reduced canalicular connectivity. Moreover, analysis of bone mineral density distribution by qBEI indicated an impaired and more heterogeneous matrix mineralization in individuals with MESD mutations than in controls. In contrast to the previously reported phenotypes of individuals with OI XX, the more severe phenotype in the present study is likely explained by a mutation in exon 2, located within the chaperone domain of MESD, that leads to a complete loss of function, which indicates the relevance of MESD in early skeletal development. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

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Section: Methodsmentioning

confidence: 99%

Compound Heterozygous Frameshift Mutations in MESD Cause a Lethal Syndrome Suggestive of Osteogenesis Imperfecta Type XX

Stürznickel

Jähn‐Rickert

Zustin

et al. 2020

Journal of Bone and Mineral Research

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“…Joint stiffness, mobility restriction, and pain may result with these alterations. 5,6 The production of osteophyte bones is influenced by a number of biological growth factors such as Transforming growth factor, a multifunctional cytokine. 7 Noninvasive radiological examinations serve an important role in the early clinical diagnosis of unresolved clinical symptoms of low back pain.…”

Section: Discussionmentioning

confidence: 99%

Bilateral bony fusion of sacroiliac joint- A rare case report

Goshi

2023

IJCAP

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SI joint dysfunction is responsible for about 15-30% of low backache causes. It is crucial for locomotor activity as well as delivery during labour. It aids in axial body weight transmission and distribution from the sacrum to the pelvis. Limited gliding movements occur within joint cavity of this synovial joint. They are a category of inflammatory illnesses that affect the vertebral spines and peripheral joints, with stiffness as a common symptom. Anatomical differences in SI joint morphology, such as auxiliary SI joint, ilio sacral complex and sacral defect, and dismorphic joint, are of compelling interest when it comes to SI joint diseases. Obese people suffer from a variety of health problems related to sacroiliac joint.

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“…In OA, osteocyte dysfunction is characterized by altered lacuna morphology and protein expressions, both of which may be the response to excessive mechanical loading. The morphological and functional aberrations then cause dysregulation of bone cells, disruption of bone and cartilage homeostasis, and OA exacerbation [ 21 , 78 , 79 ]. Hence, the cellular and molecular mechanisms behind such anomalies should be elucidated.…”

Section: Osteocyte Dysfunctionmentioning

confidence: 99%

Osteocyte Dysfunction in Joint Homeostasis and Osteoarthritis

Zhang

Wen

2021

IJMS

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Structural disturbances of the subchondral bone are a hallmark of osteoarthritis (OA), including sclerotic changes, cystic lesions, and osteophyte formation. Osteocytes act as mechanosensory units for the micro-cracks in response to mechanical loading. Once stimulated, osteocytes initiate the reparative process by recruiting bone-resorbing cells and bone-forming cells to maintain bone homeostasis. Osteocyte-expressed sclerostin is known as a negative regulator of bone formation through Wnt signaling and the RANKL pathway. In this review, we will summarize current understandings of osteocytes at the crossroad of allometry and mechanobiology to exploit the relationship between osteocyte morphology and function in the context of joint aging and osteoarthritis. We also aimed to summarize the osteocyte dysfunction and its link with structural and functional disturbances of the osteoarthritic subchondral bone at the molecular level. Compared with normal bones, the osteoarthritic subchondral bone is characterized by a higher bone volume fraction, a larger trabecular bone number in the load-bearing region, and an increase in thickness of pre-existing trabeculae. This may relate to the aberrant expressions of sclerostin, periostin, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, insulin-like growth factor 1, and transforming growth factor-beta, among others. The number of osteocyte lacunae embedded in OA bone is also significantly higher, yet the volume of individual lacuna is relatively smaller, which could suggest abnormal metabolism in association with allometry. The remarkably lower percentage of sclerostin-positive osteocytes, together with clustering of Runx-2 positive pre-osteoblasts, may suggest altered regulation of osteoblast differentiation and osteoblast-osteocyte transformation affected by both signaling molecules and the extracellular matrix. Aberrant osteocyte morphology and function, along with anomalies in molecular signaling mechanisms, might explain in part, if not all, the pre-osteoblast clustering and the uncoupled bone remodeling in OA subchondral bone.

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Multiscale bone quality analysis in osteoarthritic knee joints reveal a role of the mechanosensory osteocyte network in osteophytes

Cited by 12 publications

References 59 publications

Compound Heterozygous Frameshift Mutations in MESD Cause a Lethal Syndrome Suggestive of Osteogenesis Imperfecta Type XX

Compound Heterozygous Frameshift Mutations in MESD Cause a Lethal Syndrome Suggestive of Osteogenesis Imperfecta Type XX

Bilateral bony fusion of sacroiliac joint- A rare case report

Osteocyte Dysfunction in Joint Homeostasis and Osteoarthritis

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