Variant alleles of the Wnt antagonist FRZB are determinants of hip shape and modify the relationship between hip shape and osteoarthritis.

Objective: To test whether single-nucleotide polymorphisms (SNPs) of the FRZB gene are associated with hip shape, and to determine whether FRZB variant alleles affect the relationship between hip shape and radiographic osteoarthritis (OA) of the hip.

Methods: A nested case-control study of Caucasian women, age ≥65 years, from the Study of Osteoporotic Fractures cohort was performed. Cases (n = 451) were defined as subjects with radiographic evidence of incident hip OA during followup, while controls (n = 601) were subjects in whom no radiographic hip OA was identified at baseline or followup.

Role of bone architecture and anatomy in osteoarthritis.

When considering the pathogenesis of osteoarthritis (OA), it is important to review the contribution of bone in addition to the contribution of cartilage and synovium. Although bone clearly plays a role in determining the distribution of biomechanical forces across joints, which in turn plays a role in the initiation of OA, it has also more recently been appreciated that bone may contribute in a biological sense to the pathogenesis of OA. Far from being a static structure, bone is a dynamic tissue undergoing constant remodeling, and it is clear from a number of radiographic and biochemical studies that bone and cartilage degradation occurs hand in hand.

Effects of inflammation on bone: an update.

Purpose Of Review: To present an updated summary of the relationship between inflammation and localized and generalized bone loss in the rheumatic diseases.

Recent Findings: In addition to the well established role of inflammatory cytokines in promoting enhanced osteoclast function and bone loss, recent work has discovered the cytokine milieu may also inhibit osteoblast function and bone repair. The WNT and bone morphogenetic protein pathways provide molecular links between inflammation and altered bone homeostasis in chronic inflammatory states.

Assessment of bone remodelling in childhood-onset systemic lupus erythematosus.

Objective: To identify predictors of bone remodelling in children and young adults with SLE.

Methods: Ninety subjects with SLE aged 8-22 years underwent yearly measurements of height, bone age, bone turnover markers, serum Type I IFNs, SLEDAI and BMD. Predictors of bone turnover were examined using serum osteocalcin as a marker of bone formation and both serum tartrate-resistant acid phosphatase (TRAP) and urine N-telopeptide (NTx) as markers of bone resorption.

Active shape modeling of the hip in the prediction of incident hip fracture.

The objective of this study was to evaluate right proximal femur shape as a risk factor for incident hip fracture using active shape modeling (ASM). A nested case-control study of white women 65 years of age and older enrolled in the Study of Osteoporotic Fractures (SOF) was performed. Subjects (n = 168) were randomly selected from study participants who experienced hip fracture during the follow-up period (mean 8.

Relationship between joint shape and the development of osteoarthritis.

Purpose Of Review: To present an updated summary of the relationship between joint shape and the development of osteoarthritis, with a particular focus on osteoarthritis of the hip.

Recent Findings: Osteoarthritis of the hip is highly heritable, with a genetic contribution estimated at 60%. Among the genes that have been linked to this disease are several that are involved in the development and maintenance of joint shape, including members of the Wingless (Wnt) and the bone morphogenetic protein (BMP) family.

The messenger and the message: gp96 (GRP94)-peptide interactions in cellular immunity.

Vaccination of mice with tumor-derived stress proteins, such as Hsp70 and gp96 (GRP94), can elicit antitumor immune responses, yielding a marked suppression of tumor growth and metastasis. The molecular basis for this response is proposed to reflect a peptide-binding function for these proteins. In this view, stress proteins bind the antigenic peptide repertoire of their parent cell, and when provided to the immune system, tumor-derived stress protein-peptide complexes are processed by antigen-presenting cells (APCs) to yield the subsequent activation of tumor-directed cytotoxic T lymphocyte activity.

Glucose-regulated protein 94/glycoprotein 96 elicits bystander activation of CD4+ T cell Th1 cytokine production in vivo.

Glucose-regulated protein 94 (GRP94/gp96), the endoplasmic reticulum heat shock protein 90 paralog, elicits both innate and adaptive immune responses. Regarding the former, GRP94/gp96 stimulates APC cytokine expression and dendritic cell maturation. The adaptive component of GRP94/gp96 function reflects a proposed peptide-binding activity and, consequently, a role for native GRP94/gp96-peptide complexes in cross-presentation.

GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression.

In chemical carcinogenesis models, GRP94 (gp96) elicits tumor-specific protective immunity. The tumor specificity of this response is thought to reflect immune responses to GRP94-bound peptide antigens, the cohort of which uniquely identifies the GRP94 tissue of origin. In this study, we examined the apparent tissue restriction of GRP94-elicited protective immunity in a 4T1 mammary carcinoma model.