The new bone biology: Pathologic, molecular, and clinical correlates

Abstract

Bone and cartilage and their disorders are addressed under the following headings: functions of bone; normal and abnormal bone remodeling; osteopetrosis and osteoporosis; epithelial-mesenchymal interaction, condensation and differentiation; osteoblasts, markers of bone formation, osteoclasts, components of bone, and pathology of bone; chondroblasts, markers of cartilage formation, secondary cartilage, components of cartilage, and pathology of cartilage; intramembranous and endochondral bone formation; RUNX genes and cleidocranial dysplasia (CCD); osterix; histone deacetylase 4 and Runx2; Ligand to receptor activator of NFkappaB (RANKL), RANK, osteoprotegerin, and osteoimmunology; WNT signaling, LRP5 mutations, and beta-catenin; the role of leptin in bone remodeling; collagens, collagenopathies, and osteogenesis imperfecta; FGFs/FGFRs, FGFR3 skeletal dysplasias, craniosynostosis, and other disorders; short limb chondrodysplasias; molecular control of the growth plate in endochondral bone formation and genetic disorders of IHH and PTHR1; ANKH, craniometaphyseal dysplasia, and chondrocalcinosis; transforming growth factor beta, Camurati-Engelmann disease (CED), and Marfan syndrome, types I and II; an ACVR1 mutation and fibrodysplasia ossificans progressiva; MSX1 and MSX2: biology, mutations, and associated disorders; G protein, activation of adenylyl cyclase, GNAS1 mutations, McCune-Albright syndrome, fibrous dysplasia, and Albright hereditary osteodystrophy; FLNA and associated disorders; and morphological development of teeth and their genetic mutations.

Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats

“…Furthermore, the dynamic responses of plasma concentration of NTproCNP, growth plate expansion and growth plate content of CNPs are positively related, underpinning the view that the hormone's production is intimately involved in linear growth. Previous studies indicate that over or under CNP activity, in contrast to some other essential growth factors in cartilage (Cohen 2006), have concordant effects on the skeletal phenotype without causing skeletal deformity (Kake et al 2009, Olney et al 2009). These observations are consistent with the findings in vitro showing that CNP acts positively at multiple sites (and at different phases) of chondrogenesis -the combined effects of which greatly augment the orderly expansion (Kake et al 2009) of the growth plate.…”

Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone

“…This may account in part for the abundance of osteoclast-like multinucleated giant cells usually seen in GCTOB because NFkB together with c-fos and RANKL regulate the differentiation of osteoclasts from preosteoclasts. 17,18 Interestingly, TP73L whose protein product is p63 was among the significantly upregulated genes identified for GCTOB even though none of the earlier gene expression profiling studies on GCTOB identified p63 as being highly expressed. 15,16,19 A closer examination of the TP73L expression in this series of tumors revealed that its expression was the highest in four of the six GCTOB whereas the other two GCTOB showed similar levels of TP73L expression as seen in ABC and FD.…”

“…Many of the overexpressed genes such as RUNX2, BMP2, SPARC, TNFRSF11B and ALPL are known to be important in the process of bone resorption and formation. 18 GSEA was performed to identify specific pathways that are upregulated in individual tumor types and the NFkB pathway showed relative upregulation in GCTOB although statistical significance was not reached (P ¼ 0.08). This may account in part for the abundance of osteoclast-like multinucleated giant cells usually seen in GCTOB because NFkB together with c-fos and RANKL regulate the differentiation of osteoclasts from preosteoclasts.…”

Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro

“…The osteoblasts lying on the bone surface become quiescent (resting phase) lining cells (Hill, 1998). With the completion of normal bone formation, approximately 70% of osteoblasts can be expected to undergo apoptosis, with the rest developing into osteocytes or more frequently, the bone-lining cells (Cohen, 2006). These bone-lining, osteoblast-like cells regulate the flow of mineral ions to the bone extracellular fluid, making up the blood-bone barrier, and can even re-differentiate to osteoblasts in time of need (Seeman, 2009).…”