Heterogeneity of the osteocyte lacuno-canalicular network architecture and material characteristics across different tissue types in healing bone

Schemenz, Victoria; Gjardy, André; Chamasemani, Fereshteh Falah; Roschger, Andreas; Roschger, Paul; Zaslansky, Paul; Helfen, Lukas; Burghammer, Manfred; Fratzl, Peter; Weinkamer, Richard; Brunner, Roland; Willie, Bettina M.; Wagermaier, Wolfgang

doi:10.1016/j.jsb.2020.107616

Cited by 14 publications

(8 citation statements)

References 81 publications

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“…Conventional lacunar size and shape parameters have been calculated in this study and are consistent with previous reports ranging from 100 μm 3 to 500 μm 3 for lacunar volume [ 62 , 93 ] and lacunar sphericity ranging from 0.71 to 0.73 in shape [ 18 ]. The organization of the is displayed in Fig.…”

Section: Resultssupporting

confidence: 90%

Multiscale morphological analysis of bone microarchitecture around Mg-10Gd implants

Sefa

Espiritu

Ćwieka

et al. 2023

Bioactive Materials

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Section: Resultssupporting

confidence: 90%

Multiscale morphological analysis of bone microarchitecture around Mg-10Gd implants

Sefa

Espiritu

Ćwieka

et al. 2023

Bioactive Materials

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“…Thus, in the proband the perilacunar and peri-canalicular reservoir is likely highly loaded with calcium, which might contribute to the overall high calcium concentration found in the bone material. In line with this assumption, while we did not observe abnormalities in terms of the number/density or size of osteocyte lacunae, the proband's bone contained more circular osteocyte lacunae in 2D sections than expected, which may either be attributed to the presence of woven bone [36], and/or an altered ability of the osteocyte to model its lacunar shape due to a disturbed perilacunar remodelling apparatus. It is noteworthy that several mineralised osteocyte lacunae were also seen in our patient's bone material reflecting dead osteocytes, which indicate defective bone turnover, repair and impaired bone quality [37].…”

Section: Discussionsupporting

confidence: 85%

A case of autosomal dominant osteopetrosis type II with a severe bone phenotype but no amino acid converting mutation in the CLCN7 gene

Hofstaetter

Atkins

Kogawa

et al. 2021

Preprint

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Autosomal Dominant Osteopetrosis type II (ADOII), also known as Albers-Schönberg disease, is caused by mutation of the CLCN7 chloride channel gene and is characterized by reduced bone resorption. Here we report on an individual with the classic features of ADOII, who had a history of fractures from childhood, displayed high bone mass and characteristic “sandwich vertebrae” on x-ray. Our genetic analyses showed no amino acid converting mutation in the patient’s DNA but we did find evidence of haploinsufficiency of CLCN7 mRNA. An iliac crest bone sample from the patient revealed bone tissue and material abnormalities relative to normal controls based on quantitative backscattered electron imaging and histomorphometric analyses. Additionally to lamellar bone, we observed significant amounts of woven bone and mineralised cartilage, as well as an increased frequency and thickness (up to 15 microns) of cement lines. Giant osteoclasts with numerous nuclei were present. The bone mineralisation density distribution (BMDD) of the entire bone area revealed markedly increased average mineral content of the dense bone (CaMean T-score +10.1) and frequency of bone with highest mineral content (CaHigh T-score +19.6), suggesting continued mineral accumulation and lack of bone remodelling. Osteocyte lacunae sections (OLS) characteristics were unremarkable except the OLS shape which was unusually circular. Together, our findings suggest that the reduced expression of CLCN7 mRNA in osteoclasts, and possibly also osteocytes, causes poorly remodelled bone with abnormal bone matrix with high mineral content. This together with the lack of adequate bone repair mechanisms makes the material brittle and prone to fracture.

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“…Thus, in the proband, the perilacunar and peri-canalicular reservoir is likely highly loaded with calcium, which might contribute to the overall high calcium concentration found in the bone material. In line with this assumption, while we did not observe abnormalities in terms of the number/density or size of osteocyte lacunae, the proband’s bone contained more circular osteocyte lacunae in 2D sections than expected, which may either be attributed to the presence of woven bone [ 46 ], or an altered ability of the osteocyte to model its lacunar shape due to a disturbed perilacunar remodelling apparatus. It is noteworthy that several mineralized osteocyte lacunae were also seen in our patient’s bone material reflecting dead osteocytes, which indicate defective bone turnover, repair and impaired bone quality [ 47 ].…”

Section: Discussionsupporting

confidence: 84%

A Mild Case of Autosomal Recessive Osteopetrosis Masquerading as the Dominant Form Involving Homozygous Deep Intronic Variations in the CLCN7 Gene

et al. 2022

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Osteopetrosis is a heterogeneous group of rare hereditary diseases characterized by increased bone mass of poor quality. Autosomal-dominant osteopetrosis type II (ADOII) is most often caused by mutation of the CLCN7 gene leading to impaired bone resorption. Autosomal recessive osteopetrosis (ARO) is a more severe form and is frequently accompanied by additional morbidities. We report an adult male presenting with classical clinical and radiological features of ADOII. Genetic analyses showed no amino-acid-converting mutation in CLCN7 but an apparent haploinsufficiency and suppression of CLCN7 mRNA levels in peripheral blood mononuclear cells. Next generation sequencing revealed low-frequency intronic homozygous variations in CLCN7, suggesting recessive inheritance. In silico analysis of an intronic duplication c.595-120_595-86dup revealed additional binding sites for Serine- and Arginine-rich Splicing Factors (SRSF), which is predicted to impair CLCN7 expression. Quantitative backscattered electron imaging and histomorphometric analyses revealed bone tissue and material abnormalities. Giant osteoclasts were present and additionally to lamellar bone, and abundant woven bone and mineralized cartilage were observed, together with increased frequency and thickness of cement lines. Bone mineralization density distribution (BMDD) analysis revealed markedly increased average mineral content of the dense bone (CaMean T-score + 10.1) and frequency of bone with highest mineral content (CaHigh T-score + 19.6), suggesting continued mineral accumulation and lack of bone remodelling. Osteocyte lacunae sections (OLS) characteristics were unremarkable except for an unusually circular shape. Together, our findings suggest that the reduced expression of CLCN7 mRNA in osteoclasts, and possibly also osteocytes, causes poorly remodelled bone with abnormal bone matrix with high mineral content. This together with the lack of adequate bone repair mechanisms makes the material brittle and prone to fracture. While the skeletal phenotype and medical history were suggestive of ADOII, genetic analysis revealed that this is a possible mild case of ARO due to deep intronic mutation.

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Heterogeneity of the osteocyte lacuno-canalicular network architecture and material characteristics across different tissue types in healing bone

Cited by 14 publications

References 81 publications

Multiscale morphological analysis of bone microarchitecture around Mg-10Gd implants

Multiscale morphological analysis of bone microarchitecture around Mg-10Gd implants

A case of autosomal dominant osteopetrosis type II with a severe bone phenotype but no amino acid converting mutation in the CLCN7 gene

A Mild Case of Autosomal Recessive Osteopetrosis Masquerading as the Dominant Form Involving Homozygous Deep Intronic Variations in the CLCN7 Gene

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