Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization

Holm, Erik; Aubin, Jane E.; Hunter, Graeme; Beier, Frank; Goldberg, Harvey A.

doi:10.1016/j.bone.2014.10.007

Cited by 50 publications

(42 citation statements)

References 38 publications

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“…While we found trends towards mild reduction in most of these genes in Bsp −/− vs. WT mouse calvaria, no significant differences were identified (Supplementary Figure 1A). Osteoblast markers Alpl /TNAP and Spp1 /OPN were significantly decreased in Bsp −/− versus WT samples at 14 dpn (with similar trends at 26 dpn)(Supplementary Figure 1B), likely reflecting reduced expression of osteoblast markers reported previously in long bones (Holm et al, 2015; Malaval et al, 2008). Because Bsp −/− mice feature reduced long bone remodeling due to loss of osteoclast activation (Boudiffa et al, 2010; Malaval et al, 2008), we also assayed osteoclast markers in calvarial bones, including Acp5 (gene for tartrate resistant acid phosphatase; TRAP), Ctsk (gene for cathepsin K), and Tnfrsf11a (gene for receptor activator of NF-kB, RANK).…”

Section: Resultssupporting

confidence: 79%

“…In long bones, while chondrocyte markers were not altered by loss of BSP, changes in several osteoblast markers were noted (Bouleftour et al, 2014; Holm et al, 2015). Osteoblast markers were assayed in PSS and SOS bone by IHC, including OSX, TNAP, and OPN.…”

Section: Resultsmentioning

confidence: 97%

“…Alterations in osteoblast markers have been reported in long bones of Bsp −/− mice (Bouleftour et al, 2014; Holm et al, 2015). Osteoblast markers including OSX, TNAP, and OPN were assayed in alveolar and mandibular bone by IHC at 1 dpn.…”

Section: Resultsmentioning

confidence: 99%

“…Alterations in the epiphyseal growth plate of Bsp −/− mice have been reported at early ages, as well as low bone formation rate (Bouleftour et al, 2014; Holm et al, 2015). However, neither frank osteomalacia nor accumulation of osteoid on cortical or trabecular bone surfaces have been identified [Figure 7A-D and (Bouleftour et al, 2014; Malaval et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…In a femur cortical bone defect model, Bsp −/− mice displayed delayed bone repair (Malaval et al, 2009b; Monfoulet et al, 2010), and in a femur bone marrow ablation model, absence of BSP caused both reduced medullary trabecular bone formation and delayed osteoclastic resorption (Wade-Gueye et al, 2012). Investigations focusing on early stages of long bone development identified alterations in the growth plate, delayed initiation of mineralization, and a reduction in expression of some osteogenic markers in Bsp −/− vs. WT mice (Bouleftour et al, 2014; Holm et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

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Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

Foster¹,

Ao²,

Willoughby³

et al. 2015

Bone

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Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. In order to define the role BSP plays in the process of biomineralization of these tissues, we analyzed cementogenesis, dentinogenesis, and osteogenesis (intramembranous and endochondral) in craniofacial bone in Bsp null mice and wild-type (WT) controls over a developmental period (1-60 days post natal; dpn) by histology, immunohistochemistry, undecalcified histochemistry, microcomputed tomography (microCT), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quantitative PCR (qPCR). Regions of intramembranous ossification in the alveolus, mandible, and calvaria presented delayed mineralization and osteoid accumulation, assessed by von Kossa and Goldner's trichrome stains at 1 and 14 dpn. Moreover, Bsp−/− mice featured increased cranial suture size at the early time point, 1 dpn. Immunostaining and PCR demonstrated that osteoblast markers, osterix, alkaline phosphatase, and osteopontin were unchanged in Bsp null mandibles compared to WT. Bsp−/− mouse molars featured a lack of functional acellular cementum formation by histology, SEM, and TEM, and subsequent loss of Sharpey's collagen fiber insertion into the tooth root structure. Bsp−/− mouse alveolar and mandibular bone featured equivalent or fewer osteoclasts at early ages (1 and 14 dpn), however, increased RANKL immunostaining and mRNA, and significantly increased number of osteoclast-like cells (2-5 fold) were found at later ages (26 and 60 dpn), corresponding to periodontal breakdown and severe alveolar bone resorption observed following molar teeth entering occlusion. Dentin formation was unperturbed in Bsp−/− mouse molars, with no delay in mineralization, no alteration in dentin dimensions, and no differences in odontoblast markers analyzed. No defects were identified in endochondral ossification in the cranial base, and craniofacial morphology was unaffected in Bsp−/− mice. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp−/− molar teeth. Dissimilar effects of loss of BSP on mineralization of dental and craniofacial tissues suggest local differences in the role of BSP and/or yet to be defined interactions with site-specific factors.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

Foster¹,

Ao²,

Willoughby³

et al. 2015

Bone

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Biomimetic Elastomeric Bioactive Siloxane‐Based Hybrid Nanofibrous Scaffolds with miRNA Activation: A Joint Physico‐Chemical‐Biological Strategy for Promoting Bone Regeneration

Han

et al. 2019

Adv Funct Materials

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Rapid and efficient disease‐induced or critical‐size bone regeneration remains a challenge in tissue engineering due to the lack of highly bioactive biomaterial scaffolds. Physical structures such as nanostructures, chemical components such as silicon elements, and biological factors such as genes have shown positive effects on bone regeneration. Herein, a bioactive photoluminescent elastomeric silicate‐based nanofibrous scaffold with sustained miRNA release is reported for promoting bone regeneration based on a joint physico‐chemical‐biological strategy. Bioactive nanofibrous scaffolds are fabricated by cospinning poly (ε‐caprolactone) (PCL), elastomeric poly (citrates‐siloxane) (PCS), and bioactive osteogenic miRNA nanocomplexes (denoted PPM nanofibrous scaffolds). The PPM scaffolds possess uniform nanostructures, significantly enhanced tensile stress (≈15 MPa) and modulus (≈32 MPa), improved hydrophilicity (30–60°), controlled biodegradation, and strong blue fluorescence. Bioactive miRNA complexes are efficiently loaded into the nanofibrous matrix and exhibit long‐term release for up to 70 h. The PPM scaffolds significantly promote the adhesion, proliferation, and osteoblast differentiation of bone marrow stem cells in vitro and enhanced rat cranial defect restoration (12 weeks) in vivo. This work reports an attractive joint physico‐chemical‐biological strategy for the design of novel cell/protein‐free bioactive scaffolds for synergistic tissue regeneration.

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Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing

et al. 2019

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Clinical translation of cell‐based products is hampered by their limited predictive in vivo performance. To overcome this hurdle, engineering strategies advocate to fabricate tissue products through processes that mimic development and regeneration, a strategy applicable for the healing of large bone defects, an unmet medical need. Natural fracture healing occurs through the formation of a cartilage intermediate, termed “soft callus,” which is transformed into bone following a process that recapitulates developmental events. The main contributors to the soft callus are cells derived from the periosteum, containing potent skeletal stem cells. Herein, cells derived from human periosteum are used for the scalable production of microspheroids that are differentiated into callus organoids. The organoids attain autonomy and exhibit the capacity to form ectopic bone microorgans in vivo. This potency is linked to specific gene signatures mimicking those found in developing and healing long bones. Furthermore, callus organoids spontaneously bioassemble in vitro into large engineered tissues able to heal murine critical‐sized long bone defects. The regenerated bone exhibits similar morphological properties to those of native tibia. These callus organoids can be viewed as a living “bio‐ink” allowing bottom‐up manufacturing of multimodular tissues with complex geometric features and inbuilt quality attributes.

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Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization

Cited by 50 publications

References 38 publications

Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein

Biomimetic Elastomeric Bioactive Siloxane‐Based Hybrid Nanofibrous Scaffolds with miRNA Activation: A Joint Physico‐Chemical‐Biological Strategy for Promoting Bone Regeneration

Developmentally Engineered Callus Organoid Bioassemblies Exhibit Predictive In Vivo Long Bone Healing

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