Skeletal self-repair: stress fracture healing by rapid formation and densification of woven bone.

Unlabelled: Stress fractures of varying severity were created using a rat model of skeletal fatigue loading. Periosteal woven bone formed in proportion to the level of bone damage, resulting in the rapid recovery of whole bone strength independent of stress fracture severity.

Introduction: A hard periosteal callus is a hallmark of stress fracture healing.

PLCgamma2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2.

Excessive bone loss in arthritic diseases is mostly due to abnormal activation of the immune system leading to stimulation of osteoclasts. While phospholipase Cgamma (PLCgamma) isoforms are known modulators of T and B lymphocyte-mediated immune responses, we found that blockade of PLCgamma enzymatic activity also blocks early osteoclast development and function. Importantly, targeted deletion of Plcg2 in mice led to an osteopetrotic phenotype.

In vivo skeletal imaging of 18F-fluoride with positron emission tomography reveals damage- and time-dependent responses to fatigue loading in the rat ulna.

The skeletal response to damaging fatigue loading is not fully understood. We used (18)F-fluoride PET to describe the time course of the skeletal response following the creation of increasing levels of in vivo, fatigue-induced damage. The right forelimbs of 40 adult rats were loaded in vivo in cyclic compression to four levels of subfracture, fatigue displacement: 30, 45, 65, or 85% of fracture displacement.

Use of the rat forelimb compression model to create discrete levels of bone damage in vivo.

Skeletal responses to damage are significant for understanding the etiology of stress fractures and possibly osteoporotic fractures. We refined the rat forelimb-loading model to produce a range of sub-fracture damage levels during in vivo cyclic loading. A total of 98 right forelimbs of anesthetized, male, 5-month old Fischer rats were loaded cyclically (2 Hz) in axial compression.

Four and half lim protein 2 (FHL2) stimulates osteoblast differentiation.

Unlabelled: FHL2, a molecule that interacts with many integrins and transcription factors, was found to play an important role in osteoblast differentiation. Overexpression of FHL2 increases the accumulation of osteoblast differentiation markers and matrix mineralization, whereas FHL2 deficiency results in inhibition of osteoblast differentiation and decreased bone formation.

Introduction: Integrin-matrix interaction plays a critical role in osteoblast function.

Marrow stromal cells and osteoclast precursors differentially contribute to TNF-alpha-induced osteoclastogenesis in vivo.

The marrow stromal cell is the principal source of the key osteoclastogenic cytokine receptor activator of NF-kappaB (RANK) ligand (RANKL). To individualize the role of marrow stromal cells in varying states of TNF-alpha-driven osteoclast formation in vivo, we generated chimeric mice in which wild-type (WT) marrow, immunodepleted of T cells and stromal cells, is transplanted into lethally irradiated mice deleted of both the p55 and p75 TNFR. As control, similarly treated WT marrow was transplanted into WT mice.

Morphological and mechanical properties of caudal vertebrae in the SAMP6 mouse model of senile osteoporosis.

The senescence-accelerated mouse, strain P6 (SAMP6), is a model of senile osteoporosis with relatively low bone mineral density (BMD), low rates of bone formation and reduced long-bone bending strength. Seeking to extend previous descriptions of the SAMP6 skeletal phenotype, we assessed the morphological and mechanical properties of vertebrae from SAM mice at 4 and 12 months of age. We hypothesized that, relative to SAMR1 controls, vertebrae from SAMP6 mice have: (1) less trabecular bone, (2) increased endosteal and periosteal bone size and (3) decreased whole-bone strength.