A Tale of Bilateral Rapidly Progressive Osteoarthritis of the Hip-It Is Not Always the Steroid Injection: A Case Report.

ABSTRACT: Rapidly progressive osteoarthritis of the hip is an unusual subset of hip osteoarthritis in which a >2 mm/yr rate of joint space narrowing occurs. Rapidly progressive osteoarthritis of the hip has been associated with intra-articular steroid injection, with the incidence of rapidly progressive osteoarthritis of the hip after intra-articular steroid injection ranging from 2.8% to 21%. The occurrence of rapidly progressive osteoarthritis of the hip unrelated to intra-articular steroid injection is rare, and not frequently reported. This report presents a unique case of rapidly progressive osteoarthritis of the hip in the bilateral hips of one patient. The first hip developed rapidly progressive osteoarthritis of the hip within 6 mos after an intra-articular steroid injection. Three years later, the second hip developed rapidly progressive osteoarthritis of the hip within 4 mos without any injection or use of systemic steroid medication. The etiology of rapidly progressive osteoarthritis of the hip in the absence of intra-articular steroid injection is unclear, and this case presents the opportunity to observe the development of rapidly progressive osteoarthritis of the hip due to different causes within the same individual.

Origin of Osteoclasts: Osteoclast Precursor Cells.

Osteoclasts are multinucleated bone-resorbing cells and a key player in bone remodeling for health and disease. Since the discovery of osteoclasts in 1873, the structure and function of osteoclasts and the molecular and cellular mechanisms of osteoclastogenesis have been extensively studied. Moreover, it has been well established that osteoclasts are differentiated in vitro from myeloid cells such as bone marrow macrophages or monocytes. The concept showing that osteoclasts are derived from a specific population (named osteoclast precursor cells [OCPs]) among myeloid cells has been long hypothesized. However, the specific precursor population of osteoclasts is not clearly defined yet. A growing body of work provides evidence of the developmental origin and lifespan of murine osteoclasts, particularly in vivo. Here, we review the emerging evidence that supports the existence of OCPs and discuss current insights into their identity.

The crosstalk between MYC and mTORC1 during osteoclastogenesis.

Osteoclasts are bone-resorbing cells that undergo extensive changes in morphology throughout their differentiation. Altered osteoclast differentiation and activity lead to changes in pathological bone resorption. The mammalian target of rapamycin (mTOR) is a kinase, and aberrant mTOR complex 1 (mTORC1) signaling is associated with altered bone homeostasis. The activation of mTORC1 is biphasically regulated during osteoclastogenesis; however, the mechanism behind mTORC1-mediated regulation of osteoclastogenesis and bone resorption is incompletely understood. Here, we found that MYC coordinates the dynamic regulation of mTORC1 activation during osteoclastogenesis. MYC-deficiency blocked the early activation of mTORC1 and also reversed the decreased activity of mTORC1 at the late stage of osteoclastogenesis. The suppression of mTORC1 activity by rapamycin in mature osteoclasts enhances bone resorption activity despite the indispensable role of high mTORC1 activation in osteoclast formation in both mouse and human cells. Mechanistically, MYC induces Growth arrest and DNA damage-inducible protein (GADD34) expression and suppresses mTORC1 activity at the late phase of osteoclastogenesis. Taken together, our findings identify a MYC-GADD34 axis as an upstream regulator of dynamic mTORC1 activation in osteoclastogenesis and highlight the interplay between MYC and mTORC1 pathways in determining osteoclast activity.