Bone marrow mesenchymal stem cells (MSCs) are multipotent cells, which among other cell lineages, give rise to adipocytes and osteoblasts. Within the bone marrow, the differentiation of MSCs into adipocytes or osteoblasts is competitively balanced; mechanisms that promote one cell fate actively suppress mechanisms that induce the alternative lineage. This occurs through the cross talk between complex signaling pathways including those derived from bone morphogenic proteins (BMPs), winglesstype MMTV integration site (Wnt) proteins, hedgehogs, delta/jagged proteins, fibroblastic growth factors (FGF), insulin, insulin-like growth factors (IGF), and transcriptional regulators of adipocyte and osteoblast differentiation including peroxisome proliferator-activated receptor-gamma (PPAR gamma) and runt-related transcription factor 2 (Runx2). Here, we discuss the molecular regulation of bone marrow adipogenesis with emphasis on signals that interact with osteoblastogenic pathways and highlight the possible therapeutic implications of these interactions.

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Maintenance of healthy bone mass requires a well-coordinated balance between the ongoing processes of bone formation and bone resorption. Bone-forming osteoblasts derive from resident adult stem cells within bone marrow called bone marrow stromal cells (BMSCs). These BMSCs are multipotent and also can give rise to adipocytes, which do not contribute directly to bone formation but may influence bone remodeling through the release of bioactive signaling molecules. Chemerin is a novel adipocyte-derived signaling molecule that promotes adipocyte differentiation. In this study we examined the role of chemerin and the cognate receptors CMKLR1 and CCRL2 as determinants of osteoblast and adipocyte differentiation of the preosteoblast 7F2 cell line and of primary BMSCs. Expression and secretion of chemerin increased dramatically with adipocyte differentiation of these cells. Functionally, knockdown of chemerin or CMKLR1 expression using RNA interference abrogated adipocyte differentiation, clonal expansion, and basal proliferation of BMSCs. In contrast, knockdown of either gene was associated with increased osteoblast marker gene expression and mineralization in response to osteoblastogenic stimuli. Forced expression of the adipogenic transcription factor peroxisome proliferator-activated receptor g (PPARg) induced chemerin expression and partially rescued the loss of adipogenesis associated with chemerin or CMKLR1 knockdown in BMSCs. Taken together, these data support a novel role for chemerin/CMKLR1 signaling in regulating adipogenesis and osteoblastogenesis of bone marrow-derived precursor cells. These data reveal a potential role for this signaling pathway as a modulator of bone mass. ß

Obesity and type 2 diabetes have reached epidemic levels and account for a substantial portion of the annual health expenditures of developed nations. While there is an abundance of epidemiological evidence demonstrating that obesity is a primary risk factor for developing type 2 diabetes, the mechanism(s) underlying this linkage are not completely understood. Given the enormous impact of these disorders on global health, considerable research effort has been devoted to elucidate the pathophysiological relationship between these two disorders. Two factors believed to contribute to the causal link between obesity and type 2 diabetes are chronic inflammation and altered secretion of adipose-derived signaling molecules (adipokines). Independent lines of investigation have implicated the novel adipokine chemerin as a regulator of adipogenesis, inflammation, and glucose metabolism through interactions with the cognate cell surface receptor chemokine-like receptor 1. Increased levels of chemerin that occur with obesity are hypothesized to be a causal factor in the development of type 2 diabetes as a consequence of dysregulation of the key physiological processes regulated by this adipokine. This review summarizes current research on the biological roles of chemerin and chemokine-like receptor 1, and highlights key questions to guide future research on the role of this adipokine in mediating obesity and the development of type 2 diabetes.

Less than 200 cases of posttraumatic superficial temporal artery pseudoaneurysm have been described in the literature. The majority of these cases result from blunt head trauma and are diagnosed an average of three weeks following the inciting traumatic event. In this case report, we describe a superficial temporal artery pseudoaneurysm that developed and was diagnosed the same day of a blunt head trauma in a 54-year-old white male. This is the earliest formation/diagnosis of post-traumatic superficial temporal artery pseudoaneurysm yet reported in the literature. This case report demonstrates that this diagnosis should be kept in the list of differential diagnoses for a post-traumatic soft tissue mass of the face, even immediately following the traumatic event.