Study of Osteoclast Adhesion to Cortical Bone Surfaces: A Correlative Microscopy Approach for Concomitant Imaging of Cellular Dynamics and Surface Modifications

Shemesh, Mordechai; Addadi, Sefi; Milstein, Yonat; Geiger, Benjamin; Addadi, Lia

doi:10.1021/acsami.5b08126

Cited by 16 publications

(11 citation statements)

References 67 publications

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“…It appears that a lifetime of only a few minutes is too short for further growth and stabilization, given that the time periods required for either ring expansion ( figure 5) or ring fusion (figure 6), exceed the intrinsic lifespan of small and dynamic SZs. As a possible trigger for the growth of some SZ rings (either on the smooth surface, or more prominently on the rough bone), we have previously observed the stabilization of small SZ rings by local bone protrusions with matching size [38]. Examination of the growing rings (more than 10 mm) indicated that unlike the small rings that either grow or uniformly collapse, the growing SZs display non-uniform dynamic behaviour, containing stable and unstable segments.…”

Section: Discussionmentioning

confidence: 95%

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Surface microtopography modulates sealing zone development in osteoclasts cultured on bone

Shemesh

Addadi

Geiger

2017

J. R. Soc. Interface.

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Bone homeostasis is continuously regulated by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between these two cell populations leads to pathological bone diseases such as osteoporosis and osteopetrosis. Osteoclast functionality relies on the formation of sealing zone (SZ) rings that define the resorption lacuna. It is commonly assumed that the structure and dynamic properties of the SZ depend on the physical and chemical properties of the substrate. Considering the unique complex structure of native bone, elucidation of the relevant parameters affecting SZ formation and stability is challenging. In this study, we examined in detail the dynamic response of the SZ to the microtopography of devitalized bone surfaces, taken from the same area in cattle femur. We show that there is a significant enrichment in large and stable SZs (diameter larger than 14 mm; lifespan of hours) in cells cultured on rough bone surfaces, compared with small and fast turning over SZ rings (diameter below 7 mm; lifespan approx. 7 min) formed on smooth bone surfaces. Based on these results, we propose that the surface roughness of the physiologically relevant substrate of osteoclasts, namely bone, affects primarily the local stability of growing SZs.

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Section: Discussionmentioning

confidence: 95%

“…Polished and unpolished bone slices were scanned using an atomic force microscope (NanoWizard R 3 Bioscience, JPK Instruments, Berlin, Germany), as described in [38]. Images were taken using contact mode in liquid (cell culture media, see §2.3).…”

Section: Atomic Force Microscopy Characterization and Roughness Analysismentioning

confidence: 99%

Surface microtopography modulates sealing zone development in osteoclasts cultured on bone

Shemesh

Addadi

Geiger

2017

J. R. Soc. Interface.

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“…Osteoclasts were reported to be sensitive to topographical discontinuities that were in the tens of microns in culture matrices [21][22][23][24], but there has not yet been any clear evidence concerning the determinant factors for migration direction of such cells [24]. Possibly, odontoclast progression could be guided by micro/macro-morphological patterns on root surfaces, such as macroscopic surface curvature or surface asperities such as the micro-features resulting from PDL collagen fibre insertion and mineral crystal orientation [48], or the gradients of local mechanobiological stimulation.…”

Section: Size and Shape Characteristics Of Resorption Cratersmentioning

confidence: 99%

In vivo effects of different orthodontic loading on root resorption and correlation with mechanobiological stimulus in periodontal ligament

Zhong

Chen

Weinkamer

et al. 2019

J. R. Soc. Interface.

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Orthodontic root resorption is a common side effect of orthodontic therapy. It has been shown that high hydrostatic pressure in the periodontal ligament (PDL) generated by orthodontic forces will trigger recruitment of odontoclasts, leaving resorption craters on root surfaces. The patterns of resorption craters are the traces of odontoclast activity. This study aimed to investigate resorptive patterns by: (i) quantifying spatial root resorption under two different levels of in vivo orthodontic loadings using microCT imaging techniques and (ii) correlating the spatial distribution pattern of resorption craters with the induced mechanobiological stimulus field in PDL through nonlinear finite-element analysis (FEA) in silico. Results indicated that the heavy force led to a larger total resorption volume than the light force, mainly by presenting greater individual crater volumes ( p , 0.001) than increasing crater numbers, suggesting that increased mechano-stimulus predominantly boosted cellular resorption activity rather than recruiting more odontoclasts. Furthermore, buccal-cervical and lingual-apical regions in both groups were found to have significantly larger resorption volumes than other regions ( p , 0.005). These clinical observations are complemented by the FEA results, suggesting that root resorption was more likely to occur when the volume average compressive hydrostatic pressure exceeded the capillary blood pressure (4.7 kPa).

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“…6 Researchers termed these structures as SZ rings, actin rings, or SZs. [7][8][9][10][11][12][13][14][15] The SZ defines the resorption area of the bone, consisting of a dynamic actin-rich ring-like structure which we have designated as a sealing ring since 2007. 1,2,[16][17][18][19][20] Our recent work has shown an important role for plastins in osteoclast biology, and the formation of actin-rich SZ structures.…”

Section: Introductionmentioning

confidence: 99%

L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction

et al. 2020

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Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones (NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro. Transduction of TAT-fused full-length L-plastin peptide into osteoclasts from L-plastin knockout mice rescued the formation of nascent sealing zones and sealing rings in a time-dependent manner. This response was not observed with mutated full-length L-plastin (Ser-5 and-7 to Ala-5 and-7) peptide. In contrast to the observed defect in the NSZ, L-plastin deficiency did not affect podosome formation or adhesion of osteoclasts in vitro or in vivo. Histomorphometry analyses in 8-and 12-week-old female L-plastin knockout mice demonstrated a decrease in eroded perimeters and an increase in trabecular bone density, without a change in bone formation by osteoblasts. This decrease in eroded perimeters supports that osteoclast function is attenuated in L-plastin knockouts. Micro-CT analyses confirmed a marked increase in trabecular bone mass. In conclusion, female L-plastin knockout mice had increased trabecular bone density due to impaired bone resorption by osteoclasts. L-plastin could be a potential target for therapeutic interventions to treat trabecular bone loss.

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Study of Osteoclast Adhesion to Cortical Bone Surfaces: A Correlative Microscopy Approach for Concomitant Imaging of Cellular Dynamics and Surface Modifications

Cited by 16 publications

References 67 publications

Surface microtopography modulates sealing zone development in osteoclasts cultured on bone

Surface microtopography modulates sealing zone development in osteoclasts cultured on bone

In vivo effects of different orthodontic loading on root resorption and correlation with mechanobiological stimulus in periodontal ligament

L-Plastin deficiency produces increased trabecular bone due to attenuation of sealing ring formation and osteoclast dysfunction

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