Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts

Osteoarthritis (OA) is a degenerative disease of the hyaline articular cartilage. This disease is progressive and may lead to disability. Researchers proposed many regenerative approaches to treat osteoarthritis, including stem cells. Trans-differentiation of a fully differentiated cell state directly into another different differentiated cell state avoids the disadvantages of fully reprogramming cells to induced pluripotent stem cells (iPSCs) in terms of faster reprogramming of the needed cells. Trans-differentiation also reduces the risk of tumor formation by avoiding the iPSC state. OSKM factors (Oct4, Sox2, Klf4, and cMyc) accompanied by the JAK-STAT pathway inhibition, followed by the introduction of specific differentiation factors, directly reprogrammed mouse embryonic fibroblasts to chondroblasts. Our results showed the absence of intermediate induced pluripotent stem cell formation. The resulting aggregates showed clear hyaline and hypertrophic cartilage. Tumor formation was absent in sub-cutaneous capsules transplanted in SCID mice.

Chondroid Tumors as Incidental Findings and Differential Diagnosis between Enchondromas and Low-grade Chondrosarcomas

Chondroid tumors are a heterogeneous group of neoplasms that all share the production of chondroid matrix. This ranges from a fetal type to mature hyaline cartilage and mirrors its imaging characteristics.The benign chondroid tumors represent some of the most encountered incidental bone lesions, with osteochondroma the most frequent benign bone tumor. Enchondroma is mostly asymptomatic, and yet it is probably the second most common primary bone tumor. Similarly, its malignant counterpart, chondrosarcoma, is the second most common malignant primary bone tumor.The 2013 World Health Organization (WHO) updated this group of tumors, and grade 1 chondrosarcoma was renamed “atypical cartilage tumor” and classified as an intermediate type of tumor, not a malignancy, which better describes its clinical behavior.In this article we summarize changes made in the updated 2013 WHO classification and highlight the diagnostic features differentiating an enchondroma from a low-grade chondrosarcoma. We also describe practical imaging aspects of the remaining chondroid tumors.

Chondrosarcoma of the Mobile Spine and Sacrum

Chondrosarcoma is a rare malignant tumor of bone. This family of tumors can be primary malignant tumors or a secondary malignant transformation of an underlying benign cartilage tumor. Pain is often the initial presenting complaint when chondrosarcoma involves the spine. In the mobile spine, chondrosarcoma commonly presents within the vertebral body and shows a predilection for the thoracic spine. Due to the resistance of chondrosarcoma to both radiation and chemotherapy, treatment is focused on surgery. With en bloc excision of chondrosarcoma of the mobile spine and sacrum patients can have local recurrence rates as low as 20%.

Disseminated Liposarcoma in a Dog

A 9-year-old, female Mongrel dog was presented for posterior hindlimb weakness, inability to stand, and pain in the lumbosacral and pelvic regions. Radiography revealed a lytic lesion extending from L5 to L6 to the ilium. At necropsy, an 8 − 2 to 3.2 − 3 cm, irregular, white, firm mass was identified extending from the left dorsolateral aspect of the L6 vertebrae to the sacrum, crossing the sacroiliac joint to the ilium, and reaching the acetabulum without affecting the joint cartilage. Tumor masses were also present bilaterally near the costochondral junction of several ribs. White, soft nodules were present in the heart, pericardium, lungs, spleen, and kidneys as well. Histologically, osteolysis with disruption of the cortical bone and reactive bone with the presence of multinucleated osteoclasts was noted. Neoplastic cells consisted of variable, small basophilic round cells (SBRC) with very scant cytoplasm, larger polygonal cells with abundant eosinophilic cytoplasm, and vacuolated cells resembling adipocytes. Within the marrow cavity, vacuolated cells with necrosis predominated, whereas in periosteal areas, polygonal and vacuolated cells that were mixed with a lower percentage of SBRC were more common. In the lungs and heart, SBRC predominated, and in the spleen, polygonal cells were more numerous. Tumor cells stained positive for vimentin and S-100 and stained negative for CD99, neuron-specific enolase, synaptophysin, chromogranin A, cytokeratins, desmin, myoglobin, and actin. This tumor most likely arose from the marrow cavity of the L6 and later invaded through the vertebral body into adjacent vertebrae and various visceral sites.

Post-traumatic osteochondroma of the calcaneus

Osteochondroma is the most common bone and cartilage tumor. It is usually congenital but may be related to trauma. A case of osteochondroma affecting the calcaneus, an unusual location for this lesion, is presented. Surgical excision appears to be as effective a cure in this location as in others.