Analysis of mouse models with loss or mutations in Nbr1 demonstrate an age-dependent high bone mass due to altered osteoblast activity

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S43
Author(s):  
C.A. Whitehouse⁎ ◽  
S. Waters ◽  
K. Marchbank ◽  
A. Horner ◽  
N. McGowan ◽  
...  
Keyword(s):  
Bone Mass ◽  
Mouse Models ◽  
High Bone Mass ◽  
Osteoblast Activity ◽  
Age Dependent ◽  
High Bone

scholarly journals In Vivo Analysis of Wnt Signaling in Bone

Endocrinology ◽  
2007 ◽  
Vol 148 (6) ◽  
pp. 2630-2634 ◽  
Author(s):  
Donald A. Glass ◽  
Gerard Karsenty
Keyword(s):  
Bone Mass ◽  
Wnt Signaling ◽  
Bone Remodeling ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Osteoclast Differentiation ◽  
Wnt Signaling Pathway ◽  
Human Beings ◽  
High Bone Mass ◽  
High Bone

Bone remodeling requires osteoblasts and osteoclasts working in concert to maintain a constant bone mass. The dysregulation of signaling pathways that affect osteoblast or osteoclast differentiation or function leads to either osteopenia or high bone mass. The discovery that activating and inactivating mutations in low-density lipoprotein receptor-related protein 5, a putative Wnt coreceptor, led to high bone mass and low bone mass in human beings, respectively, generated a tremendous amount of interest in the possible role of the Wnt signaling pathway in the regulation of bone remodeling. A number of mouse models have been generated to study a collection of Wnt signaling molecules that have been identified as regulators of bone mass. These mouse models help establish the canonical Wnt signaling pathway as a major regulator of chondrogenesis, osteoblastogenesis, and osteoclastogenesis. This review will summarize these advances.

scholarly journals Loss of BMPR2 leads to high bone mass due to increased osteoblast activity

2015 ◽  
Vol 128 (7) ◽  
pp. 1308-1315 ◽  
Author(s):  
J. W. Lowery ◽  
G. Intini ◽  
L. Gamer ◽  
S. Lotinun ◽  
V. S. Salazar ◽  
...  
Keyword(s):  
Bone Mass ◽  
High Bone Mass ◽  
Osteoblast Activity ◽  
High Bone

Loss of BMPR2 leads to high bone mass due to increased osteoblast activity

Development ◽  
2015 ◽  
Vol 142 (8) ◽  
pp. e0805-e0805
Author(s):  
J. W. Lowery ◽  
G. Intini ◽  
L. Gamer ◽  
S. Lotinun ◽  
V. S. Salazar ◽  
...  
Keyword(s):  
Bone Mass ◽  
High Bone Mass ◽  
Osteoblast Activity ◽  
High Bone

scholarly journals Mice lacking DKK1 in T cells exhibit high bone mass and are protected from estrogen deficiency-induced bone loss

iScience ◽  
2021 ◽  
pp. 102224
Author(s):  
Juliane Lehmann ◽  
Sylvia Thiele ◽  
Ulrike Baschant ◽  
Tilman D. Rachner ◽  
Christof Niehrs ◽  
...  
Keyword(s):  
T Cells ◽  
Bone Loss ◽  
Bone Mass ◽  
Estrogen Deficiency ◽  
High Bone Mass ◽  
High Bone

scholarly journals Osteoarthritis: Insights Offered by the Study of Bone Mass Genetics

2021 ◽  
Vol 19 (2) ◽  
pp. 115-122
Author(s):  
A. Hartley ◽  
C. L. Gregson ◽  
L. Paternoster ◽  
J. H. Tobias
Keyword(s):  
Bone Mass ◽  
Causal Effect ◽  
Mendelian Randomisation ◽  
Mineral Density ◽  
High Bone Mass ◽  
Increased Risk ◽  
High Bone ◽  
Genetic Mechanisms ◽  
Additional Support

Abstract Purpose of Review This paper reviews how bone genetics has contributed to our understanding of the pathogenesis of osteoarthritis. As well as identifying specific genetic mechanisms involved in osteoporosis which also contribute to osteoarthritis, we review whether bone mineral density (BMD) plays a causal role in OA development. Recent Findings We examined whether those genetically predisposed to elevated BMD are at increased risk of developing OA, using our high bone mass (HBM) cohort. HBM individuals were found to have a greater prevalence of OA compared with family controls and greater development of radiographic features of OA over 8 years, with predominantly osteophytic OA. Initial Mendelian randomisation analysis provided additional support for a causal effect of increased BMD on increased OA risk. In contrast, more recent investigation estimates this relationship to be bi-directional. However, both these findings could be explained instead by shared biological pathways. Summary Pathways which contribute to BMD appear to play an important role in OA development, likely reflecting shared common mechanisms as opposed to a causal effect of raised BMD on OA. Studies in HBM individuals suggest this reflects an important role of mechanisms involved in bone formation in OA development; however further work is required to establish whether the same applies to more common forms of OA within the general population.

scholarly journals Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
April Hartley ◽  
Sarah A. Hardcastle ◽  
Monika Frysz ◽  
Jon Parkinson ◽  
Lavinia Paternoster ◽  
...  
Keyword(s):  
Bone Mass ◽  
Functional Limitations ◽  
Functional Limitation ◽  
Hip Osteoarthritis ◽  
Joint Space ◽  
Mineral Density ◽  
High Bone Mass ◽  
High Bone ◽  
Subchondral Sclerosis

Abstract Background Individuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis). As the role of bone mineral density (BMD) in hip OA progression is unclear, we aimed to determine if individuals with HBM have increased incidence and/or progression of bone-forming OA sub-phenotypes. Methods We analysed an adult cohort with and without HBM (L1 and/or total hip BMD Z-score > + 3.2) with pelvic radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Superior/inferior acetabular/femoral osteophyte and medial/superior joint space narrowing (JSN) grades were summed and Δosteophyte and ΔJSN derived. Pain and functional limitations were quantified using the WOMAC questionnaire. Associations between HBM status and change in OA sub-phenotypes were determined using multivariable linear/logistic regression, adjusting for age, sex, height, total body fat mass, follow-up time and baseline sub-phenotype grade. Generalised estimating equations accounted for individual-level clustering. Results Of 136 individuals, 62% had HBM at baseline, 72% were female and mean (SD) age was 59 (10) years. HBM was positively associated with both Δosteophytes and ΔJSN (adjusted mean grade differences between individuals with and without HBM βosteophyte = 0.30 [0.01, 0.58], p = 0.019 and βJSN = 0.10 [0.01, 0.18], p = 0.019). Incident subchondral sclerosis was rare. HBM individuals had higher WOMAC hip functional limitation scores (β = 8.3 [0.7, 15.98], p = 0.032). Conclusions HBM is associated with the worsening of hip osteophytes and JSN over an average of 8 years, as well as increased hip pain and functional limitation.

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